Various lipids and their functions
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These books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\\n\\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\\n\\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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IntechOpen and Knowledge Unlatched formed a partnership to support researchers working in engineering sciences by enabling an easier approach to publishing Open Access content. Using the Knowledge Unlatched crowdfunding model to raise the publishing costs through libraries around the world, Open Access Publishing Fee (OAPF) was not required from the authors.
\n\nInitially, the partnership supported engineering research, but it soon grew to include physical and life sciences, attracting more researchers to the advantages of Open Access publishing.
\n\n\n\nThese books synthesize perspectives of renowned scientists from the world’s most prestigious institutions - from Fukushima Renewable Energy Institute in Japan to Stanford University in the United States, including Columbia University (US), University of Sidney (AU), University of Miami (USA), Cardiff University (UK), and many others.
\n\nThis collaboration embodied the true essence of Open Access by simplifying the approach to OA publishing for Academic editors and authors who contributed their research and allowed the new research to be made available free and open to anyone anywhere in the world.
\n\nTo celebrate the 50 books published, we have gathered them at one location - just one click away, so that you can easily browse the subjects of your interest, download the content directly, share it or read online.
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Lipids function as important storage compounds to maintain cellular activities. Lipids store high reducing power and energy since those biosynthetic processes require high amount of reducing cofactors and ATP. Storage lipids do not cause any chemical effect on cellular activity such as osmolarity, pH and ion strength because of its hydrophobicity. Membrane lipids such as phospholipids, carotenoids, and cholesterols play a housekeeping role. In addition, some of lipids function as protein modifiers or signaling molecules.
Recently, plant oils are gathering keen interest as a source of renewable energy according to rapid increase in social demands for establishing a low-carbon-society. However, oil production for biofuels and biorefinery using higher plants and crops is strongly worried for competing with food production and to increase those market prices. Therein, algae came into play a new oil-producing organism since algae do not compete with food production. According to their high productivity per unit area, prokaryotic photoautotrophs such as cyanobacteria and eukaryotic algae such as protists are expected to become a promising feedstock in future (Gong & Jiang, 2011).
Although numerous kinds of lipids exist in nature, main carbon chain of the molecules is almost derived from limited numbers of precursor molecules such as fatty acids and isoprenoids. Interestingly, some parts of the synthetic pathways of lipids are quite different among animals, higher plants, cyanobacteria and some eukaryotic microalgae. Although there is quite few information on lipid biosynthesis and metabolism in algae, it is noteworthy that most of biosynthetic pathways of hydrocarbons such as fatty acid- and isoprene-derived hydrocarbon have been well characterized in microalgae.
In this chapter, we will introduce recent progresses on lipid and hydrocarbon biosynthetic pathways in microalgae: First, unique features of algal lipid synthetic pathways mostly hypothesized by advanced DNA sequencing technique although those are not well proved experimentally yet. Second, two factors for hydrocarbon biosynthesis in microalgae characterized recently by a combination of expressed sequence tags (EST) analysis and novel enzyme characterization. Those are: (1) decarbonylase to produce fatty acid-derived hydrocarbons in cyanobacteria and (2) isoprene-derived hydrocarbon biosynthetic pathway in a representative oil-producing colonial microalga,
Although there is no agreed definition and classification of “lipids” (The AOCS Lipid Library, http://lipidlibrary.aocs.org/), here we define a term “lipid” as follows: 1) it is biological component of and derived from organisms; 2) it is basically very soluble in organic solvents but not in water; 3) it contains hydrocarbon group in its structure. We adopt biosynthetic classification to categorize lipids such as fatty acid, isoprene or others of unique lipids as shown in Table 1, instead of a conventional lipid classification such as simple lipid, derived lipid, complex lipid, and so on. Here we used the term “lipids” for compounds composed of only carbon, hydrogen, and oxygen.
Table 1 indicates the list of various lipids and their functions. Although numberless lipids exist in nature, main carbon chain of the molecules is mostly derived from fatty acids, isoprenes and their homologous compounds via some synthetic pathways. Recent progress in genome/transcriptome sequencing technology and its computational analysis on similarity of those base sequences among organisms, namely
\n\t\t\t\t\t | \n\t\t\t\t\n\t\t\t\t\t | \n\t\t\t\t\n\t\t\t\t\t | \n\t\t\t
Fatty acid | \n\t\t\tC2n-/straight-carbon chainwith carboxyl group | \n\t\t\tMembrane component;Bioactivity | \n\t\t
Polyketide | \n\t\t\tVarious carbon chain with polyketone group | \n\t\t\tAntibiotic; Bioactivity | \n\t\t
Glyceride | \n\t\t\tEster of fatty acid & glycerol | \n\t\t\tCommon storage lipid | \n\t\t
Terpenoid | \n\t\t\tC5n-/branched-carbon chain;isoprene derivate | \n\t\t\tBioactivity | \n\t\t
Steroid | \n\t\t\tTri-terpenoid derivate | \n\t\t\tCommon hormone | \n\t\t
Carotenoid | \n\t\t\tTetra-terpenoid derivate;conjugated double bond; absorbent | \n\t\t\tPigment | \n\t\t
Various lipids and their functions
Acetyl-coenzyme A (CoA) is a universal carbon donor for fatty acid biosynthesis. Acetyl-CoA is supplied via multiple paths from various origins and then subsequently metabolized into malonyl-acyl carrier protein (ACP) by sequential reactions. One molecule of ATP (1ATP) is used for the carboxylation of acetyl unit to produce one malonyl unit. In general, fatty acid biosynthesis utilizes acetyl-CoA and malonyl-ACP as starting substrates and acetyl unit donors. Primarily, butyryl(C4)-ACP is synthesized from acetyl(C2)-CoA and malonyl(C3)-ACP via sequential reactions of condensation, decarboxylation, and reduction of non-malonyl-ACP derived keto unit. Two molecules of NADPH (2NADPH) is used for the reduction of keto group. Accordingly, 1ATP and 2NADPH are consumed to elongate chain of fatty acid molecule by adding C2-saturated carbon unit in fatty acid biosynthesis. Acyl-ACP is elongated up to acyl(C16 or 18)-ACP. Molecules with C2n-carbon chain are widely distributed among various organisms and those of C2n-1-carbon chain are synthesized from C2n-compounds by carbon-loss (Řezanka & Sigler, 2009). In bacteria,
In any step, a synthesized carbon chain can be metabolized into various products including glycerolipids, triacylglycerides (TG), phospholipids and glycolipids (Joyard et al., 2010). Fatty acids synthesized excessively are stored as TG in most eukaryotes. Usually prokaryotes do not accumulate TG although
Same fatty acids as metabolites are widely observed in various organisms but their biosynthetic pathways are different depending on classification. There are four known groups of enzyme(s) for fatty acid biosynthesis; type-I fatty acid synthase (FAS), type-II FAS, particular elongases, and enzymes for catalyzing the reversal of ß-oxidation. Typically, animals and fungi possess type-I FAS which is a large multi-functional enzyme with multiple functional domains (Chan & Vogel, 2010; Joyard et al., 2010). Bacteria, plastids and mitochondria have type-II FAS which is composed of four subunit proteins such as ß-ketoacyl-ACP synthase (KAS), ß-ketoacyl-ACP reductase, ß-hydroxyacyl-ACP dehydratase and enoyl-ACP reductase (Chan & Vogel, 2010; Joyard et al., 2010; Hiltunen et al., 2010). A trypanosomatid
One of model organism
C18-Fatty acid can be further elongated via the fatty acid elongation pathway. Fatty acid elongation process is very similar to that of the fatty acid synthesis although acyl-CoA and malonyl-CoA are used as a substrate. In the process, 1ATP and 2NADPH are required for C2-unit elongation of saturated carbon chain since CoA-activation is not essential as suggested by another study (Hlousek-radojcic et al., 1998). Fatty acid elongation reaction site was shown to be located in the endoplasmic reticulum (Kunst & Samuels, 2009). In contrast to FAS system, all known elongation systems are basically compatible and functions simultaneously. Fatty acid elongase constitutes an enzyme complex of four subunits which is similar to type-II FAS; namely, ß-ketoacyl-CoA synthase (KCS), ß-ketoacyl- CoA reductase, ß-hydroxyacyl-CoA dehydratase and enoyl-CoA reductase. There are two different KCSs; namely “elongation of very long-chain fatty acid” (ELOVL or merely ELO)-type elongase which contributes to sphingolipid biosynthesis and “fatty acid elongation” (FAE)-type elongase which contributes to plant seed TG or wax biosynthesis (Venegas-Calerón et al., 2010). Typically, animals and fungi possess ELO-type while land plants possess FAE-type. In some cases, ELO and FAE subunits are inaccurately referred as mere “elongase” since heterologous expression of single gene for KCS often results in successful elongation of acyl-CoA by the help of the other subunit of the host (typically, yeast and land plant
Poly unsaturated very long-chain fatty acid (PUVLCFA, PULCA, VLC-PUFA, etc.) is one of elongated fatty acids (e.g. Arachidonic acid, Eicosapentaenoic acid, and Docosahexaenoic acid). PUVLCFA is commonly observed in algae such as Euglenophytes, diatoms (
Polyketide includes various complex compounds such as antibiotics (e.g. erythromycin, tetracycline, lovastatin) (Staunton & Weissman, 2001). Polyketide biosynthesis is similar to C4 and longer fatty acid synthesis except successive reduction of
There are three types of polyketide syntheses (PKSs): type-I PKS which is a large multi-functional enzyme in the consequence of multiple functional domains, type-II PKS which is composed of monofunctional proteins to form complex and type-III PKS which resembles chalcone synthase catalyzing the committed step in flavonoid biosynthesis in higher plants and some bryophytes (Shen, 2003). Type-I PKSs are further classified into two, namely iterative and non-iterative (modular) types. Bacteria possess type-I to III of PKSs. Fungi and animal typically possess type-I iterative PKS which is closely related each other (Jenke-Kodama & Dittmann, 2009). Interestingly, there is evolutional connection between PKSs and FASs (Jenke-Kodama & Dittmann, 2009; John et al., 2008; Sasso et al., 2011).
In the genomes of chlorophyta (
Terpenoid which is composed of branched C5n carbon unit are synthesized by condensation of C5 isoprene units (as isopentenyl diphosphate (IPP) and its isomer dimethylallyl diphosphate (DMAPP)
Pathway for terpenoid biosynthesis
Primary and terminal molecules are underlined respectively. Substrates multiply used are shown in bold. [1]: putative Isoprene transporter. [2]: a predicted junction from the pentose phosphate pathway to the MEP pathway in cyanobacteria. AACT, acetoacetyl-CoA thiolase; CMK, 4-(cytidine 5’-diphospho)-2-C- methylerythritol kinase; DXR, 1-deoxy-D-xylulose 5-phosphate reductoisomerase; DXS, 1-deoxy-D-xylulose 5-phosphate synthase; HDR, 4-hydroxy-3-methylbut-2-en-1-yl diphosphate reductase; HDS, 4-hydroxy-3-methylbut-2-en-1-yl diphosphate synthase; HMGS, 3-hydroxy-3-methylglutaryl-CoA synthase; HMGR, 3-hydroxy-3-methylglutaryl-CoA reductase; IDI, isopentenyl diphosphate:dimethylallyl diphosphate isomerase; MCT, 2-C-methyl-D-erythritol 4-phosphate cytidylyltransferase; MDS, 2-C-methyl-D-erythritol 2,4-cyclodiphosphate synthase; MVD, mevalonate-5-diphosphate decarboxylase; MVK, mevalonate kinase; PMK, 5-phosphomevalonate kinase.
IPP and DMAPP are metabolically conjugated by condensation and dephosphorylation to produce polyterpenoid. No ATP or reducing power is required when isoprene units get into condensation reaction by head-to-tail conjunction (e.g. farnesyl pyrophosphate formation while 1NADPH is required in case of tail-to-tail condensation (e.g. squalene formation). Polyterpenoid is individually or cooperatively synthesized either in the cytosol, plastid or mitochondrion (Bouvier et al., 2005; Joyard et al., 2009; Lohr et al., 2012). Each terpenoid condensation enzyme has particular specific to isoprene molecules such as mono-/sesqui-/di-/tri-/tetra-terpene, respectively. Unlikely land plant, the biosynthesis of isoprene in green macroalgae proceeds via MEP pathway in the plastid (Lohr et al., 2012) and it functions to produce special natural products such as bioactive halogenated poly terpenoid (Moore, 2006). Vanadium bromoperoxidase is an abundant enzyme to produce brominated products in all classes of marine macroalgae and vanadium iodoperoxidase is also identified and characterized (Moore, 2006). However, vanadium chloroperoxidase is not yet identified despite the abundance of chlorinated compounds in algae. These haloperoxidases catalyze both halogenation and cyclization to produce various unique halogenated cyclic terpenoid in macrolagae, but such unique isoprene condensing enzyme is not yet identified in microalgae (Sasso et al., 2011).
\n\t\t\t\t\t | \n\t\t\t\t\n\t\t\t\t\t | \n\t\t\t\t\n\t\t\t\t\t | \n\t\t\t
Odd-chain fattyhydrocarbon | \n\t\t\tHydrocarbonfrom fatty acid (C2n-1) | \n\t\t\tUnknown | \n\t\t
Wax ester | \n\t\t\tEster of fatty acid & fatty alcohol | \n\t\t\tCuticle component | \n\t\t
Alkenones | \n\t\t\t\n\t\t\t\t | \n\t\t\tStorage lipid? | \n\t\t
Heterocyst glycolipid | \n\t\t\tAlcohol-/ketone-glycoside | \n\t\t\tCell wall component | \n\t\t
Even-chain fatty hydrocarbon | \n\t\t\tHydrocarbon from fatty acid (C2n) | \n\t\t\tUnknown | \n\t\t
Olefinichydrocarbon | \n\t\t\tHydrocarbon from fatty acidwith multiple double bonds | \n\t\t\tUnknown | \n\t\t
Terpenoid hydrocarbon | \n\t\t\tHydrocarbon from terpenoid | \n\t\t\tUnknown | \n\t\t
Lipids and hydrocarbons for renewable energy source
Table 2 shows a list of lipids and hydrocarbons which can be candidates for renewable energy sources. These compounds are metabolites derived from the elemental lipids shown in Table 1. Their pool sizes of metabolites in cells and production capability largely varies among species and even strains of a certain species. The most extreme example can be seen in a colonial oil-producing green alga
Microalgal species/strains nominated as oil-producer are simply classified into three groups by their main products: namely, hydrocarbons, TG/free fatty acids and the other lipids. For example, bacteria (Schirmer et al., 2010), a unicellular green alga
Alliphatic carbon-chain is a ubiquitous structure which exists in the molecules produced via fatty acid biosynthesis in organisms. In this part we introduce some fatty acid derivatives and their molecular properties and biosynthetic pathways.
Bacteria, microalgae and land plants produce odd-chain hydrocarbons (Řezanka & Sigler, 2009; Tornabene, 1981). Plant wax constitutes of odd-chain hydrocarbons without any branching, namely fatty hydrocarbons (Jetter & Kunst, 2008). This type of hydrocarbons is suggested to be produced via the decarbonylation pathway (Jetter & Kunst, 2008; Schirmer et al., 2010). First, acyl-CoA is reduced to form fatty aldehyde using 1NADPH as a reductant cofactor (Schirmer et al., 2010; Willis et al., 2011). In pea, the decarbonylation reaction is catalyzed by a membrane-bound enzyme, fatty acyl-CoA reductase (Cheesbrough & kolattukudy, 1984; Vioque & Kolattukudy, 1997) which is also present in the race A of
A cyanobacterium
Wax esters consist of fatty acids (acyl-CoAs
At least five species of haptophyceae (
The heterocyst of cyanobacterium
The bacterium
Olefinic hydrocarbons contain many unsaturated bonds in the molecule.
A colonial green alga
The race B hydrocarbons are methylsqualene and botryococcene which are specifically produced by
In Table 3 and Fig. 1, lipid and hydrocarbon biosynthetic pathways are summarized. All hydrocarbons are produced from precursors (namely acyl-ACP or IPP/DMAPP) which are produced from three primary metabolites; acetyl-CoA, pyruvate and GAP. GAP should be the primary metabolite during photosynthesis and transported into the cytosol. Then acetyl-CoA and pyruvate are sequentially produced from GAP in the glycolysis. On the other hand, acetyl-CoA is primarily produced by the degradation of various lipids via β-, α-, and ω- oxidation (Graham & Eastmond, 2002). Any pathway for hydrocarbon production includes decarboxylation of carbon chain supplied as substrate and consumption of ATP and reducing power (see the MVA/MEP pathway and glycolysis in Fig. 1). GAP production mostly depends on carbon fixation rate by the photosynthetic C3 cycle and the process seems to be the most effective limiting factor for hydrocarbon production. Gene expression level for fatty acid synthesis is relatively higher in race A (fatty hydrocarbon) than race B (terpenoid hydrocarbon) in
Supply of inorganic and organic carbon sources, nutrient deficiency and low-temperature are empirically known to be stimulating factors for lipid biosynthesis. Enrichment of CO2 as inorganic carbon source stimulated lipid biosynthesis and cell growth by accelerating photosynthetic carbon fixation in microalgae (Kumar et al., 2010). Neutral lipid production and accumulation was strongly accelerated in the presence of exogenous organic carbon source by accompanying with abolishing chlorophylls in a unicellular green alga
\n\t\t\t\t\t | \n\t\t\t\t\n\t\t\t\t\t | \n\t\t\t\t\n\t\t\t\t\t | \n\t\t\t\t\n\t\t\t\t\t | \n\t\t\t|
\n\t\t\t\t | \n\t\t||||
Fatty acid biosynthesis (C2) | \n\t\t\tacyl(n)-ACP + acetyl-CoA (+ CO2) + ATP + 2NADPH + 2H+→ acyl(n+2)-ACP (+ CO2) + H2O + CoA + ADP + Pi + 2NADP+\n\t\t\t | \n\t\t\tFatty acid(C4~18) | \n\t\t\tReference pathway | \n\t\t|
Fatty acid biosynthesis (C2) | \n\t\t\tacyl(n)-CoA + acetyl-CoA + 2NADPH + 2H+→ acyl(n+2)-CoA + H2O + CoA + 2NADP+\n\t\t\t | \n\t\t\tFatty acid(C4~16) | \n\t\t\t\n\t\t\t\t mitochondria | \n\t\t|
Fatty acid biosynthesis (C2) | \n\t\t\tacyl(n)-CoA + acetyl-CoA + 2NADPH + 2H+→ acyl(n+2)-CoA + H2O + CoA + 2NADP+\n\t\t\t | \n\t\t\tFatty acid(C4~18) | \n\t\t\tEngineered | \n\t\t|
MVApathway (C5) | \n\t\t\t3acetyl-CoA + H2O + 3ATP + 2NADPH + 2H+→ IPP + 3CoA + CO2 + 3ADP +Pi + 2NADP+ ; IPP ⇌ DMAPP | \n\t\t\tIsoprene | \n\t\t\tReference pathway | \n\t\t|
MEP pathway (C5) | \n\t\t\tpyruvate + GAP + ATP + CTP + NADPH + 4e- + 5H+→ IPP (DMAPP) + CO2 + 2H2O + ADP + CMP + PPi + NADP+\n\t\t\t | \n\t\t\tIsoprene | \n\t\t\tIncomplete about redox | \n\t\t|
\n\t\t\t\t | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t | |
Fatty acid elongation (C2) | \n\t\t\tacyl(n)-CoA + acetyl-CoA (+ CO2) + ATP + 2NADPH + 2H+→ acyl(n+2)-CoA (+ CO2) + H2O + CoA + ADP + Pi + 2NADP+\n\t\t\t | \n\t\t\tFatty acid(C20~28) | \n\t\t\tReference pathway | \n\t\t|
Fatty acid elongation (C2) | \n\t\t\tacyl(n)-CoA + acetyl-CoA + 2NADPH + 2H+→ acyl(n+2)-CoA + H2O + CoA + 2NADP+\n\t\t\t | \n\t\t\tFatty acid(C6~16) | \n\t\t\tHuman mitochondria | \n\t\t|
Head-to-tail isoprene condensation (C5) | \n\t\t\t(n)isoprene → Poly terpenoid-PP + (n-1)PPi (n≥2) | \n\t\t\tTerpenoid | \n\t\t\tReference reaction | \n\t\t|
Head-to-head isoprene condensation (C5) | \n\t\t\t2 isoprene + NADPH → Poly terpenoid + 2PPi + NADP+ + H+\n\t\t\t | \n\t\t\tHydro- carbon | \n\t\t\tReference reaction | \n\t\t|
\n\t\t\t\t | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t | |
Fatty aldehyde formation | \n\t\t\tacyl-CoA + NADPH + H+\n\t\t\t\t → fatty aldehyde + CoA + NADP+\n\t\t\t | \n\t\t\tFatty- aldehyde | \n\t\t\tReference reaction | \n\t\t|
Fatty aldehyde formation | \n\t\t\tacyl-ACP + NADPH + H+\n\t\t\t\t → fatty aldehyde + ACP + NADP+\n\t\t\t | \n\t\t\tFatty- aldehyde | \n\t\t\tCyanobacteria | \n\t\t|
Alcohol formation | \n\t\t\tacyl-CoA + 2NADPH + 2H+ → fatty alcohol + CoA + 2NADP+\n\t\t\t | \n\t\t\tFatty- alcohol | \n\t\t\tReference reaction | \n\t\t|
Alcohol formation | \n\t\t\tfatty aldehyde + NADPH + H+\n\t\t\t\t → fatty alcohol + NADP+\n\t\t\t | \n\t\t\tFatty- alcohol | \n\t\t\tReference reaction | \n\t\t|
\n\t\t\t\t | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t | |
Aldehyde decarbonylation | \n\t\t\tfatty aldehyde(n) → fatty hydrocarbon(n-1) + CO | \n\t\t\tHydro- carbon | \n\t\t\tReference reaction | \n\t\t|
\n\t\t\t\t | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t | |
Alcohol reduction | \n\t\t\tfatty alcohol (n) → fatty hydrocarbon (n) | \n\t\t\tHydro- carbon | \n\t\t\tIncomplete about redox | \n\t\t|
\n\t\t\t\t | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t | |
Head-to-head acyl-CoA condensation | \n\t\t\t2acyl-CoA(n) → alkadiene (2n-1) + CO2 + H2O + 2CoA | \n\t\t\tHydro- carbon | \n\t\t\tIncompletely understood | \n\t\t|
\n\t\t\t\t | \n\t\t\t\n\t\t\t | \n\t\t\t | \n\t\t | |
Fatty acid/alcohole sterification | \n\t\t\tfatty acyl-CoA(X) + fatty alcohol(Y) → wax ester (X+Y) + CoA | \n\t\t\tWax ester | \n\t\t\tReference reaction | \n\t\t
Carbon flow, consumption of ATP and reducing power in lipid and hydrocarbon biosynthetic pathways
Carbon flow, consumption of ATP and reducing power in lipid biosynthetic pathways. Black- or blue-chained spheres indicate C-C chain. Orange- or Yellow-colored circles indicate Pi in various compounds including IPP, DMAPP, ATP and so on. Difference in color of box-frames indicates difference in localization of pathways. Fatty acid biosynthesis in engineered
Recent
Genetic engineering in eukaryotic algae is important technology to be established although it still is quite challenging (Gong et al., 2011; Radakovits et al., 2010). It is highly expected that algal oil is efficiently produced with high purity since it is produced by enzymatic reactions in homogenous productive cells. So, characteristics of products, such as chain length and number of double bond in the molecule, can be modified by genetic engineering (Gong & Jiang, 2011; Radakovits et al., 2010). Further, facilitation of lipid extraction (e.g. lipid auto-secretion from cells to the medium) (Cho & Cronan, 1995; Liu et al., 2010; Michinaka et al., 2003; Nojima et al., 1999) and cell precipitation control (Kawano et al., 2011)) are important to be improved since such processes consume vast energy at industrial process of production. It is noteworthy that direct extraction of oil from
Finding of limiting step in whole photosynthetic CO2 fixation process is also important to increase lipid productivity. Algae have evolved by developing ability to facilitate the utilization of ambient level of CO2 by the action of innate CO2 concentrating mechanisms (Giordano et al., 2005; Raven, 2010). Exogenous CO2 supplementation recovers cells from CO2-limitation when cells are exposed such conditions within few hours. However, the photosynthetic activity quickly changes to optimize their ability to exposed conditions since algal cells possess ability to adapt/acclimate to environmental change. The maximal carbon fixation rate and high-CO2 tolerance are highly depend on microalgal species/strain and therefore CO2-enrichment is not so beneficial for the improvement of cost and energy performance of microalgal production (Baba & Shiraiwa, 2012). Further investigation is necessary to produce newly-engineered algal cells which exhibit high and efficient CO2-utilization and -fixation ability with enhanced photosynthesis and lipid productivity.
This work was financially supported, in part, by a Grant-in-Aid for Scientific Research from the Core Research of Evolutional Science & Technology (CREST) program from the Japan Science and Technology Agency (JST) (to YS).
As defined by the US Environmental Protection Agency (EPA) [1], an endocrine-disrupting chemical (EDCs) is “an exogenous agent that interferes with synthesis, secretion, transport, metabolism, binding action, or elimination of natural blood-borne hormones that are present in the body and are responsible for homeostasis, reproduction, and developmental process.” Diamanti-Kandarakis et al. [2] among thousands of human-made chemicals, almost 1000 chemicals may have endocrine-disrupting properties [3]. Initially, it was thought that EDCs deploy their actions mainly through various nuclear hormone receptors like estrogen receptors (ERs), progesterone receptors (PRs), androgen receptors (ARs) and thyroid receptors. However, as research progressed on EDCs and their mechanism of actions, it is now known that they can also act on non-nuclear receptors, nonsteroid receptors, orphan receptors and other enzymatic pathways related to metabolism, cancer and other physiological processes [2].
As the compounds classified under EDCs are from dispersed heterogeneous sources, they can be divided into two major classes, synthetic and natural. Synthetic EDCs include industrial solvents and their byproducts [dioxins, polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), alkylphenols etc.], agricultural pesticides [methoxychlor (MTX), chlorpyrifos, dichlorodiphenyltrichloroethane (DDT)], fungicides, herbicides, insecticides, plasticizers [phthalates, bisphenol A (BPA)] and pharmaceuticals [diethylstilbestrol (DES)] whereas, phytoestrogens (genistein, coumestrol etc.) are grouped under natural sources of EDCs. Humans are exposed to the broad range of EDCs mainly through the dietary intake (fish, meat, dairy and poultry products) and to some extent by inhalation and dermal uptake [2, 4]. Mostly EDCs are highly lipophilic, and they tend to get accumulated in the adipose tissues [5, 6]. They can accumulate in human and other large mammals’ fatty tissues through biomagnification and bioaccumulation as they are the top predators in the food chain [7]. Due to their long half-life, they remain stored in the adipose tissues for years. Persistent Organic Pollutants (POPs) are the best example of long term accumulations in human tissues [8]. However, plasticizers like BPA have a very short estimated half-life of about four hours. Instead of bioaccumulation, they generally get excreted via urine [9]. Still, BPA has a very adverse effect on the human endocrine system due to their continuous exposure throughout the days [10].
Among the vast range of chemicals under EDCs, some are referred to as “obesogens” as they promote or induce weight gain in individuals by altering endocrine pathways involved in metabolism, energy homeostasis and appetite. The phthalates, perfluorinated compounds, BPA, dioxins, and some pesticides showed obesogenic potentials [11, 12]. Though their mechanism of action is not very well understood, some report indicated that these chemicals might act through Peroxisome proliferator-activated receptor gamma γ (PPAR-γ), a ligand-activated transcription factor, has a role in various cellular functions as well as glucose homeostasis, lipid metabolism, and prevention of oxidative stress [13, 14]. Some suggest they may act via the thyroid axis, as the thyroid hormone is a crucial regulator of metabolism [15, 16]. Hence, this field is relatively new and emerging in EDC’s research and needs further studies.
The prevalence of obesity and associated diseases like type 2 diabetes, cardiovascular diseases, metabolic syndromes and cancers are progressively increasing at an alarming rate in recent years. Globally the cases of obesity have nearly tripled since 1975. As per a WHO report, in 2016, 13% of adults aged 18 or more are obese worldwide. A more recent report stated that approximately thirty-eight million children (under five years) are obese. In simple language, obesity can be defined as an “abnormal or excessive fat accumulation that may impair health” [17]. The measure of obesity is generally done by body mass index (BMI), defined as a person’s weight in kilograms divided by the square of his/her height in meters (kg/m2). A BMI of 30 or greater falls within the obese range; the limit changes to 25 or more in Asian populations [18, 19]. It is a widely accepted fact that the primary cause of obesity is the imbalance between calory intake and energy expenditure. However, obesity is a complex disease caused mainly by endocrine disruption, which also involves interaction between genetic and environmental factors.
The Obesogen Hypothesis suggests that environmental chemicals, characterized as “obesogens,” induce obesity by enhancing the engagement, differentiation and size of adipocytes, by altering metabolic setpoints or modifying the hormonal control of appetite and satiety [20]. Many EDCs are obesogens in nature and found abundantly in our environment, which may induce adipogenesis and lipid accumulation in the tissues. About 50 of such compounds have been identified to date [20]. Various mechanisms of action of the obesogens are discussed later in this chapter.
Obesogens have peculiar characteristics which make them potential to interfere with various endocrine and metabolic pathways. They are believed to be xenohormones as they imitate or partially resemble natural hormones and have unwanted physiological effects. They can bind to endocrine receptors present on the cell membrane, cytosol, or nucleus, thereby altering their natural functions [21]. Along with the structural similarities with native hormones, their ability to do this also relies on its lipophilicity and small molecular weight. Partition coefficient, half-life and molecular weight are the three main components of xenohormones. A partition coefficient (P) is “the ratio of the concentration of a substance in one medium or phase (C1) to the concentration in a second phase (C2) when the two concentrations are at equilibrium; that is, partition coefficient = (C1/C2)equal.” [22]. This is how the distribution efficiency of a chemical is measured between two mediums. Here in obesogen’s case, it is between the tissue and blood. A compound’s octanol–water partition coefficient expresses that (KOW), referred to the ratio of a chemical’s concentration in the octanol phase to its concentration in the aqueous phase of a two-phase octanol/water system [23]. It is an essential measure of its lipophilicity of a chemical. The bioaccumulation and toxicity of a chemical largely depend upon KOW. As being organic, obesogens are naturally lipophilic compound, which means they have a higher KOW value. More the value of the KOW of a compound, the more will be its tendency to accumulate in the adipose tissues [24].
Now, coming to the half-life, the biological half-life of a chemical is the time it takes to break down or eliminate half of the chemical’s quantity from the body. In the body, a longer biological half-life implies longer endurance. Ideally, obesogens have longer biological half-lives means a short exposure can have life-long consequences [25]. The last of the three properties, molecular weight, refers to the size of a compound molecule. Small molecules can diffuse more readily through adipocytes. However, many large molecules having high molecular weight can give rise to smaller metabolites which may have a similar effect to obesogens [24]. The bioaccumulation and the binding affinity for the receptors largely depend upon these three criteria. Many obesogens perfectly fit into these criteria. Moreover, some of them are also resistant to degradation [e.g. 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47)] [21]. A summary of some well-known obesogens with their characteristics is listed in Table 1.
Source | Obesogens | Chemical characteristics | ||
---|---|---|---|---|
Log KOW | Biological Half-life | Mol. weight | ||
Industrial | BPA | 3.32 | 21.3 +/− 7.4 h [26] | 228.29 g/mol |
Bisphenol S (BPS) | 1.65 | 6.8 ± 0.7 h [27] | 250.27 g/mol | |
BDE-47 | 6.76 [28] | 664 days [29] | 485.79 g/mol | |
3,3′,4,4′-Tetrachlorobiphenyl (PCB-77) | 6.72 | 1.2 Months [30] | 292 g/mol | |
bis(2-ethylhexyl) phthalate (DEHP) | 7.6 | 12 hours [31] | 390.6 g/mol | |
Dioxin | 6.8 | 5.8 years [32] | 322 g/mol | |
Perfluorooctanoic acid | 4.81 | 12.6 days | 414.07 g/mol | |
Pesticides/insecticides | Dichlorodiphenyl-trichloroethane (DDT) | 6.91 | 7 years [33] | 354.5 g/mol |
Tributyltin (TBT) | 3.1–4.1 [34] | 23–30 days [35] | 290.1 g/mol | |
Atrazine | 2.61 | 10.8–11.2 hours [36] | 215.68 g/mol | |
Pharmaceuticals | Diethylstilbestrol (DES) | 5.07 | 2–3 days [37] | 268.3 g/mol |
Nicotine | 1.17 | 2 h [38] | 162.23 g/mol |
Chemical characteristics of some obesogens.
Note: All values are acquired from the PubChem database otherwise mentioned.
Though the mechanism of obesogens’ actions in inducing obesity is not very clear, some studies suggest few mechanisms by which obesogen could act. This disruption of lipid homeostasis by obesogen may involve several mechanisms, some of which are as follows (Figure 1):
increasing the adipocytes number,
increasing the size of the adipocytes,
altering endocrine regulation of adipose tissue development,
changing hypothalamic regulation of appetite and satiety
altering basal metabolic rate and energy homeostasis
altering insulin sensitivity at the organ level
Mechanisms of obesogen actions.
Obesogens generally disturb the endocrine system by interfering with PPARγ and other hormone receptors like estrogen receptor, androgen receptors and glucocorticoid receptors. PPARγ is one of the primary regulators of adipogenesis. It is highly expressed in adipose tissues and induce differentiation of adipocytes by promoting lipogenic enzymes. Along with adipogenesis, it activates genes involved in maintaining energy balance. Upon activation, PPARγ forms a heterodimer complex with nuclear receptor 9-cis retinoic acid receptor (RXR) an act as promoters for the genes required for storage of fatty acid and repression of lipolysis. That is why this PPARγ:RXR heterodimer is called the “master regulator of adipogenesis” [39]. Obesogen tributyltin (TBT) acts as a ligand and show high binding affinity with PPARγ and nuclear receptor RXR. By activating PPARγ and RXR, it might promote adipogenesis and lipid dysbiosis [40, 41]. Obesogens like spirodiclofen and quinoxyfen activate PPARγ while others like fludioxonil activate RXR [13]. Phthalates are also known activators of PPARγ, as they are shown to promote 3 T3-L1 cells to adipocytes differentiation [42]. Obesogen can increase the amount of adipose tissue by increasing the size as well as numbers of adipocytes. They can induce the Mesenchymal Stem Cells (MSCs) to differentiate into preadipocytes and adipocytes [43]. In vitro assays show numerous compounds with obesogenic properties can induce the Mesenchymal Stem Cells (MSCs) to differentiate into preadipocytes and adipocytes via PPARγ dependent pathways. TBT exposure to 3 T3-L1 preadipocytes induces them to differentiate into white adipose tissues (WAT) [44]. Bisphenol A (BPA), combined with insulin, can accelerate the conversion of 3 T3-L1 fibroblasts to adipocytes [45]. Even prenatal exposure to TBT in mouse shows preferential differentiation of MSCs towards the adipose lineage [43] (Figure 2).
PPARγ-RXR mediated action of obesogens.
From the studies available so far, it is evident that any ligand which can bind to PPARγ can induce adipogenesis and can be called obesogens. However, as human adipose tissue stores many of them, they can have a more significant cumulative effect. These additive effects are not well studied yet.
Obesogens are reported to act via other hormone receptors like estrogen receptor, androgen receptors and glucocorticoid receptors. Many studies have reported that they act via the nuclear hormone receptor-mediated pathways. Molecular cross talks with other signaling pathways have also been reported. Steroid hormones have an essential role in lipid storage and disposition of body fat. Estrogen based hormone replacement therapy is prescribed to women at their menopause to remodel their adipose depot. Foetal or neonatal exposure to phytoestrogens may induce obesity in later stages of life. Well-known phytoestrogen genistein, commonly found in soy-based foods, affects adipose tissue deposition in a dose-dependent and gender-specific manner [46].
Neonatal exposure of DES to female mice led to weight gain in adulthood. However, this effect can be sex-biased. While some EDCs may act directly via cellular steroid receptors by inducing estrogen synthesis, other EDCs may act indirectly. It is established that adipose tissue is a site of estrogen synthesis. The adipocyte cytoplasm contains the enzyme cytochrome P450 aromatase, which plays a vital role in converting estrogen from androgen. It is now reported that several EDCs can impair intracellular aromatase activity [47]. This action may raise intracellular estrogen levels in adipocytes and lead to obesity irrespective of the sexes [48]. It is reported that TBT can directly reduce the activity of the aromatase enzyme in adipose tissue at high doses, leading to reduced estradiol levels and down-regulation of the ER target genes. TBT also has an inhibitory effect on 11β-hydroxysteroid dehydrogenase 2, which leads to reduced inactivation of cortisol. It is believed that increased glucocorticoid levels could influence adipocyte differentiation and regulation of metabolism [40].
Some obesogens, especially the persistent organic pollutants (POPs), act via the ligand-activated transcription factor aryl hydrocarbon receptor (AhR). AhR activates xenobiotic-metabolizing enzyme cytochrome P450s. They can promote adipogenesis indirectly by changing PPARγ expression.
In some recent studies, researchers found that they are not linked to activation of any nuclear hormone receptors; instead, they followed some novel mechanisms, which make their mechanism of action more complex. Those include epigenetic modifications, impairment of thermogenesis and dysbiosis in gut microbiota. Some of these mechanisms will be discussed in the following sections. Some recent studies correlated COVID-19 pandemic to the obesogenic exposures, that is also being discussed in this chapter.
Epigenetics is defined as the study of heritable changes in phenotype resulting from environmentally influenced modifications of genome. Epigenetic modification can alter gene expression during development and cellular differentiation in response to environmental factors such as chemical contaminants. These modifications include DNA methylation at cytosine residues of 5′ to guanine sites (CpG sites), chemically modifying histone proteins and noncoding RNAs interference [49]. DNA methylation was considered a key mechanism responsible for adult diseases with developmental origins [50]. DNA methylation changes are responsible for the transgenerational effects of exogenous exposed individuals to chemicals and nutrition deficits [51]. For instance, the obesogen pesticide TBT induced changes in DNA methylation and histone modification invitro. Various reports have documented the environmental chemicals, including obesogens, led to an epigenetic modification in vivo and obesogen phenotype even in unexposed generations. TBT exposure in 3 T3-L1 mice preadipocytes invitro resulted in increased adipocyte differentiation along with decreased DNA methylation levels. Increased differentiation level towards the adipogenic lineage was observed in adipose-derived stromal cells (ADSCs) isolated from TBT exposed mice perinatally but at the cost of decreased osteogenesis. ADSCs exposed to TBT were associated with increased adipogenesis marker genes, such as PPARγ target gene Fapb4, where methylation level decreased in the promoter region. However, PPARγ mRNA levels were increased, but DNA methylation at its promoter region had no effects [43]. A possible reason for this lack of epigenetic regulation might be that EDC exposure during differentiation process causes DNA histone demethylation. Ultimately, PPARγ, which is under the control of H3K27me3, causes the gene to be promptly up-regulated. Importantly, prenatal exposure to TBT has been recently shown to cause the transgenerational inheritance of adiposity. It remains to be determined whether these transgenerational effects are related to permanent changes in DNA methylation profiles or other epigenetic processes.
Recent advances found in understanding adipocyte function was the presence of thermogenic brown adipose tissue (BAT) in adult human beings in a dispersed manner, not as found in concentrated discrete depots in human infants. Another discovery of white adipose tissue can also be induced to produce thermogenic fat called beige or brite fat. Increased mitochondria production is responsible for differentiation of both bona fide brown adipocytes and beiging of white adipocytes. This thermogenesis relies on the capacity to dissipate energy in the form of heat through uncoupling of cellular oxidative phosphorylation and ATP synthesis via Uncoupling protein 1 (UCP1) or sometimes through shivering. Some of the evidence has documented how some obesogens impede the production and function of thermogenic adipocytes. For instance, perinatal exposures to DDT in mice have long term-effects on thermogenesis regulation in their female offspring. When female offspring reached up to 6 months of age, they showed reduced energy expenditure & ultimately decreased thermogenesis capacity. However, no change in their physical activity was observed. Thermogenesis impairment was due to the decreased expression of PPAR-γ co-activator 1α (Ppargc1a), a master regulator for thermogenesis related genes and type 2 iodothyronine deiodinase (DiO2) (the enzyme that catalyzes thyroid hormone T4 to convert into T3 which stimulates BAT thermogenesis) [52]. Secondly, Shoucri and his colleagues [49] found that TBT or rexinoids have inhibited adipocytes’ production. Other EDCs increase thermogenesis by changing mRNA and protein levels of UCP-1. Adult mice exposed to PFOA and PFOS through diet (containing 0.02% w/w) for ten days exhibited BAT mitochondria activation for increased oxidative capacity and protein levels of UCP-1, resulting in decreased depots size of adipose tissue. PFOA exposure (80–40 μM) during in-vitro experiments activates UCP1 similarly as fatty acids. These examples indicate how obesogens influence obesity by impairing thermogenesis during the in-vitro and in vivo study. This intriguing area of obesogen epidemic and their mechanism remains to be elucidated. Through their Horizon 2020 programme, the European Union has funded several grants to establish new assays to assess EDCs effects on metabolic-end points and identify those chemicals that affect thermogenesis [53].
The gut microbiome is defined as “the totality of microorganisms, bacteria, viruses, protozoa, and fungi, and their collective genetic material present in the gastrointestinal tract” by molecular biologist Joshua Lederberg. Obesogen exposure could lead to obesity by altering the gut microbiome, a relatively novel mechanism which leads to obesity. It is well understood that obesity is correlated with gut microbiome composition [54]. Some experimental data shows that the transplant of gut microbe from obese mice can induce obesity in lean mice [55]. Conversely, the gut microbiome transplant from lean donors improved the metabolic disorder condition in obese mice [56]. It is evident from several experimental data that many obesogens induce the gut microbiome dysbiosis in zebrafish [57], mice [58] and human [59]. In mice, gut microbial dysbiosis was associated with increased fat accumulation or impaired lipid metabolism after exposure to triphenyl phosphate. Tributyltin exposure induces gut microbiome dysbiosis with increased body weight gain and dyslipidemia in mice [58]. Though, it is not yet apparent whether this metabolic disruption is a result of the gut microbiota dysbiosis or not.
Additionally, some microbial metabolites have also been reported as AhR agonists and antagonists [60, 61], as we are already aware that activating AhR inhibits adipogenesis. In contrast, inhibition of the activity leads to obesity and fatty liver disease. Two basic dietary emulsifiers, carboxymethylcellulose and P-80, were reported to initiate intestinal inflammation and gut microbiota dysbiosis, which led to metabolic disorder and increased body weight in mice [62]. These pieces of evidence suggest that inducing obesity via gut microbiota dysbiosis is possibly a potent mechanism for the obesogens to follow. However, to get more clues, this field needs to be studied further extensively.
The current outbreak of novel coronavirus has emerged as a worldwide pandemic in the past year, which is related to the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) in 2003 and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in 2012 [63]. Interestingly, a study in 2003 found a positive correlation between air pollution and extreme SARS in the Chinese population. Patients with SARS from regions with a high air pollution index (API) were twice as likely as those from regions with low APIs to die from SARS [64]. A finding based on US population found that long-term exposure to air pollution resulted in a 6% rise in cardiopulmonary mortality risk. Some of these pollutants are potent obesogenic [65].
Human studies have even shown nitrogen dioxide (NO2), one of the components of air pollution, is correlated with higher fasting serum lipids among obese individuals, indicating that obesity can worsen the effects of air pollution [66]. Animal studies have also shown that air pollution particles’ sensitivity early in life will contribute to increased visceral obesity, insulin tolerance, and inflammation, signaling NO2’s function as an endocrine disruptor [67]. Since COVID-19 is similar to SARS in causing respiratory disease, exposure to NO2 can increase the mortality rate of patients with COVID-19. However, future studies are needed to validate this relationship.
One of the most intriguing results in EDCs field came when a series of reports were published by Skinner and colleagues showing EDCs, including DDT and MTX, induce transgenerational obesogenic effects. During F1 generation, prenatally exposed individuals with anti-androgenic fungicide vinclozolin or estrogenic pesticide MTX were associated with disease in various organs in their F4 generation [68]. Similarly, when pregnant mice (FO generation) were exposed to environmentally relevant doses (nM) of TBT through drinking water, then effects on obesity were observed in F1-F3 descendants of exposed animals [69]. Notably, in a similar experiment, the pharmacological obesogen, Rosiglitazone, which can activate PPARγ, could not produce the same transgenerational obesity effects suggesting that different pathways in addition to PPARγ were required to generate transgenerational phenotype [69].
In addition to TBT effects on obesity, Skinner lab has shown several environmental chemicals such as plasticizer (BPA, DEHP, DBP) [70], pesticides MTX [71], a mixed hydrocarbon mixture (jet fuel JP-8) [72] and the widely used pesticide DDT [73], induced transgenerational obesity in a rat model as observed in F3/F4 offspring of ancestral prenatal or perinatal obesogen exposed-FO individuals [71, 72, 73]. Although molecular mechanisms underlying transgenerational inheritance of obesity are currently controversial, researchers belonging to the EDC field believe that these obesogen effects are inherited in an epigenetic manner. This point has got stronger resistance in the genetics sphere [74].
Epidemiological studies are of considerable significance for the association of disease effects with exposure to obesogens. Few cohort-based studies are available to date on the effect of obesogens in human populations. Since a considerable amount of evidence indicate that prenatal exposures predispose patients to obesity, epidemiological research concentrates on obesogenic measurements throughout pregnancy. Increase in child adiposity in multiple birth cohorts was associated with prenatal exposure to PFAS. At the same time, sexual dimorphism was sometimes linked with it [75, 76, 77, 78, 79]. A metapopulation analysis, including ten cohorts, suggests a 25% and 0.1 unit increase in weight and BMI, respectively, per ng/ml of PFOA concentration in maternal blood [80].
A research found that rising concentrations of maternal urinary phthalate during gestation doubled the risk of the offspring becoming overweight or obese [81]. Cohort research on the impact of prenatal BPA exposure has also been correlated with increased waist circumference, BMI, and risk of obesity [82]. Studies of prenatal exposure to phthalates and bisphenols have not shown a consistent association with measures of childhood adiposity compared to studies of prenatal exposure to PFAS [83]. Two studies on the American population showed an association between serum concentrations of PFAS and weight gain irrespective of sexes [84]. PFAS, particularly perfluorooctane sulfonate (PFOS) and perfluorononanoic acid (PFNA), were linked with alteration in metabolic rate [85].
Few studies have explored the longitudinal impacts on postnatal growth of prenatal exposure to other chemicals. Evidence risen over the past five years indicates that exposure to phthalates leads to adult weight gain, with most research conducted in women. Some studies by the Women’s Health initiative reported a strong correlation between urine concentrations of phthalate metabolites and weight gain [86]. Again, it is to be considered that the effect of a single chemical mostly reflects the epidemiological studies conducted. However, naturally, obesogens ploy cumulative effect as mixtures. The WAT is the depot of obesogens in the human body. More studies should be designed to estimate the accumulative effect of mixtures in future.
In vitro models have several advantages over other model systems. Taking human cells lines for the study can be of great significance considering the physiological relevance. For screening new chemicals for potential obesogenic properties, in vitro studies are generally conducted before animal models. Several cell lines are used to study the obesogenic impacts of several compounds. Among the in vitro models, mouse embryo pre adipocyte 3 T3-L1 has been used extensively to check the effects of obesogens like TBT [87], BPA [88], BPS [89], genistein [90], phthalate [91], nonylphenol [92] and so on. Other cell lines include C2C12 (mice muscle cells) [93], HELA (human cervical cancer cells) [93], HEK293C (human embryonic kidney cells) [94], HepG2 (human liver carcinoma cells) [95], hASCs (human adipose-derived stem cells) [96], C57BL/6 (mice bone marrow stromal cells) [97], hESCs (human embryonic-derived stem cells) [98] etc.
Though animal models are not recommended to study certain chemicals’ obesogenic potential, they do not mimic the human physiological systems. Still, in vivo model systems have certain advantages over in vitro systems as whole-body kinetics and systemic effects can be studied using animal models. Complex linked pathways involving multiple organs, including adipose tissue, liver, pancreas, muscle, brain, etc., regulate metabolism and weight. In understanding the role of chronic inflammation and hormone interference, in vivo experiment is particularly relevant. The most widely used animal model for the study of obesogens is rodents. Multiple obesogens including TBT [69], BPA [99], triphenyltin [100], DEHP [101], DES [102], polycyclic aromatic hydrocarbons, DDT, and nicotine, have been defined as murine models. Mice are identical biologically and anatomically to humans and share many common diseases. It is incredibly useful for diseases with an inflammatory condition, such as obesity, as animal models can mimic complex inflammatory responses. A transgenic model like obese or lean bodied mice can also be created by manipulating required genes. Other commonly used in vivo models include rats [103], zebrafish [104] and drosophila [105]. Many insights into possible obesogens and various modes of action were provided using in vivo models to investigate endocrine disruption. They may not replicate human physiology, as discussed earlier. Mice exposed to a specified amount of one particular molecule over weeks sometimes does not reflect a chronic variable exposure in humans to multiple chemicals over the years. In detecting obesogens and discerning mechanisms of action, animal models play an essential role. However, they should be combined to draw the most reliable conclusions with knowledge from in vitro studies and epidemiological studies.
The obesity epidemic first continues in the US and afterwards expands worldwide; therefore, it becomes a dire need to understand the predisposition and related disorders’ mechanisms. It becomes of utmost importance to study the extent to which the obesogen exposure influences obesity in humans and establishes the risk factors related to obesity. The risk factors include oxidative stress, inflammation, disrupted circadian rhythms, mitochondrial dysfunction and dietary composition. These interactions may be critical in the effects of obesogen exposure. Evidence documented in the obesogen research area shows that their effect mainly depends on the level and timing of exposure, especially critical windows of exposure during fetal development. Hence, it is crucial to reduce or avoid exposure to obesogens, specifically during pregnancy. However, there is no technique to determine if the individuals have been exposed to any obesogens during their development. It will be a “Holy grail” to identify biomarkers of exposure in obesogen research and establish links among obesogen exposure and other factors related to obesity. The obesogen hypothesis opened a new field into obesity by linking EDCs research with developmental disease origin. The obesogen hypothesis is still in the dearth of research. It requires more studies in the mechanism, developmental time windows and diet interaction. The effects of obesogens are related to epigenetics.
However, we still need more research to understand the mechanism and how the effects get transmitted to forthcoming generations. For instance, how does the obesogen exposure of pregnant Fo female mice lead to obesity in upcoming F3 and F4 unexposed males? There is an extreme lack of data on how obesogen exposure programs adipose tissue dysfunctional that could readily store but not mobilize fat. The obesogen sphere is almost 15 years old only. Much has been studied related to potential effects of EDCs and obesogens. The most substantial evidence for chemical obesogens existence may be the variety of pharmaceuticals that have the side effects of making patients obese. Several international and national workshops have been held to understand the potential role of EDCs in obesity and related metabolic disorders [53]. Thus, various policies and strategies should investigate the magnitude of environmental obesogenic pollutants on the obesity epidemic and the regulatory actions required on such chemicals to improve public health.
The majority of evidence that indicates the role of EDCs in driving obesity provides a mechanistic explanation of the obesity epidemic and a management strategy. The role of exogenous chemicals in growing rates of obesity through gene expression regulation (such as PPARs), hormone changes, and inflammation is supported by ample evidence. While overeating, combined with lack of exercise, is undoubtedly a significant contributor to the increase in obesity that can be addressed by decreased calorie intake and increased exercise, it may be that reducing exposure to obesogenic EDCs may also contribute to reducing obesity in the population, especially during the early stages of life. More knowledge of obesogenic pathways will improve prophylactic and therapeutic strategies. The extensive exposure of the human population to so many EDCs with obesogenic action needs evaluation. In vitro models are useful screening devices for detecting and testing obesogenic mechanisms, notably, changes in gene expression or molecular pathways. Improvements to these models will improve human extrapolation in vitro to in vivo as well. However, animal models remain a valuable and typically physiologically precise method for studying obesogenic inter-organ pathways, including hormone interference and inflammation. More epidemiological studies should be made to confirm in vitro and in vivo animal models and provide unparalleled insight into human obesogen exposures and effects. Integrating the data collected from all three of these model systems would result in better-informed choices of compounds that can be used to replace obesogens in food production, packaging, etc. It will, essentially, reduce the economic burden of obesity.
All authors thank Banaras Hindu University, India, for providing necessary resources and support to write the present chapter with the support from University Grant Commission (UGC)-Junior Research Fellowship to AM, PG and AS. This work received no external funding from any agency.
The author declares that there is no conflict of interest.
All authors listed have made a substantial contribution to this chapter. Moreover, special thanks to PG for writing some sections and proofreading the whole manuscript. Thanks to RKS for reviewing the manuscript before the final submission.
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Applying FMEA in clinical approaches can lead to a significant reduction of the risk priority number (RPN).",book:{id:"9808",slug:"contemporary-topics-in-patient-safety-volume-1",title:"Contemporary Topics in Patient Safety",fullTitle:"Contemporary Topics in Patient Safety - Volume 1"},signatures:"Hoda Sabati, Amin Mohsenzadeh and Nooshin Khelghati",authors:[{id:"340486",title:"M.Sc.",name:"Hoda",middleName:null,surname:"Sabati",slug:"hoda-sabati",fullName:"Hoda Sabati"},{id:"348872",title:"M.Sc.",name:"Amin",middleName:null,surname:"Mohsenzadeh",slug:"amin-mohsenzadeh",fullName:"Amin Mohsenzadeh"},{id:"348874",title:"MSc.",name:"Nooshin",middleName:null,surname:"Khelghati",slug:"nooshin-khelghati",fullName:"Nooshin Khelghati"}]},{id:"69876",title:"Leadership Styles in Nursing",slug:"leadership-styles-in-nursing",totalDownloads:3157,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Recent developments in the field of management-organization and organizational behavior and new concepts have also led to the emergence of new leadership styles in leadership. Leadership in health services is important for following innovations and adapting to current situations. Nurses working together with other health personnel in hospitals providing health services constitute an important group in leadership. Nursing, which is a key force for patient safety and safe care, is a human-centered profession, and therefore leadership is a key skill for nurses at all levels. The leadership styles of nurse managers are believed to be an important determinant of job satisfaction and persistence of nurses. The need for nurses with leadership skills and the need for nurses to develop their leadership skills are increasing day by day. There are several leadership styles defined in nursing literature. These leadership styles are examined under the titles of relational leadership style, transformational leadership, resonant leadership, emotional intelligence leadership, and participatory leadership. The task-focused leadership style is explored under the headings of transactional and autocratic leadership, laissez-faire leadership, and instrumental leadership.",book:{id:"9047",slug:"nursing-new-perspectives",title:"Nursing",fullTitle:"Nursing - New Perspectives"},signatures:"Serpil Çelik Durmuş and Kamile Kırca",authors:null},{id:"58916",title:"Factors Affecting the Attitudes of Women toward Family Planning",slug:"factors-affecting-the-attitudes-of-women-toward-family-planning",totalDownloads:8548,totalCrossrefCites:9,totalDimensionsCites:18,abstract:"Everyone has the right to decide on the number and timing of children without discrimination, violence and oppression, to have the necessary information and facilities for it, to access sexual and reproductive health services at the highest standard. Deficient or incorrect family planning methods, wrong attitudes and behaviors toward the methods and consequent unplanned pregnancies, increased maternal and infant mortality rates are the main health problems in most countries. Individuals’ learning modern family planning methods and having positive attitude for these methods may increase the usage of these methods and contributes the formation of healthy communities. It is considered important to examine the current attitudes and determinants in order to spread the choice of effective method.",book:{id:"6142",slug:"family-planning",title:"Family Planning",fullTitle:"Family Planning"},signatures:"Nazli Sensoy, Yasemin Korkut, Selcuk Akturan, Mehmet Yilmaz,\nCanan Tuz and Bilge Tuncel",authors:[{id:"216377",title:"Prof.",name:"Nazli",middleName:null,surname:"Sensoy",slug:"nazli-sensoy",fullName:"Nazli Sensoy"},{id:"216589",title:"Dr.",name:"Yasemin",middleName:null,surname:"Korkut",slug:"yasemin-korkut",fullName:"Yasemin Korkut"},{id:"216595",title:"Dr.",name:"Selcuk",middleName:null,surname:"Akturan",slug:"selcuk-akturan",fullName:"Selcuk Akturan"},{id:"216596",title:"Dr.",name:"Canan",middleName:null,surname:"Tuz",slug:"canan-tuz",fullName:"Canan Tuz"},{id:"216598",title:"Dr.",name:"Bilge",middleName:null,surname:"Tuncel",slug:"bilge-tuncel",fullName:"Bilge Tuncel"},{id:"216599",title:"Dr.",name:"Mehmet",middleName:null,surname:"Yilmaz",slug:"mehmet-yilmaz",fullName:"Mehmet Yilmaz"}]},{id:"69631",title:"Cultural Practices and Health Consequences: Health or Habits, the Choice Is Ours",slug:"cultural-practices-and-health-consequences-health-or-habits-the-choice-is-ours",totalDownloads:902,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Human beings are social animals with an innate desire to conform to socially accepted norms and values. Over periods of time, some of these norms become standards that all members of the community are expected to adhere to. Deviance from these standards is seen as absurd, wrong, or frankly abnormal. However, many of these cultural mores have no scientific basis and, some of them actually promote behaviors with negative health consequences. This chapter examines the cultural practices of some communities in Africa and their health consequences and, explores ways to address the challenges.",book:{id:"9138",slug:"public-health-in-developing-countries-challenges-and-opportunities",title:"Public Health in Developing Countries",fullTitle:"Public Health in Developing Countries - Challenges and Opportunities"},signatures:"Radiance Ogundipe",authors:[{id:"302308",title:"Dr.",name:"Radiance",middleName:null,surname:"Ogundipe",slug:"radiance-ogundipe",fullName:"Radiance Ogundipe"}]},{id:"55808",title:"The Role of Legumes in Human Nutrition",slug:"the-role-of-legumes-in-human-nutrition",totalDownloads:5433,totalCrossrefCites:63,totalDimensionsCites:109,abstract:"Legumes are valued worldwide as a sustainable and inexpensive meat alternative and are considered the second most important food source after cereals. Legumes are nutritionally valuable, providing proteins (20–45%) with essential amino acids, complex carbohydrates (±60%) and dietary fibre (5–37%). Legumes also have no cholesterol and are generally low in fat, with ±5% energy from fat, with the exception of peanuts (±45%), chickpeas (±15%) and soybeans (±47%) and provide essential minerals and vitamins. In addition to their nutritional superiority, legumes have also been ascribed economical, cultural, physiological and medicinal roles owing to their possession of beneficial bioactive compounds. Research has shown that most of the bioactive compounds in legumes possess antioxidant properties, which play a role in the prevention of some cancers, heart diseases, osteoporosis and other degenerative diseases. Because of their composition, legumes are attractive to health conscious consumers, celiac and diabetic patients as well as consumers concerned with weight management. The incorporation of legumes in diets, especially in developing countries, could play a major role in eradicating protein-energy malnutrition especially in developing Afro-Asian countries. Legumes could be a base for the development of many functional foods to promote human health.",book:{id:"5963",slug:"functional-food-improve-health-through-adequate-food",title:"Functional Food",fullTitle:"Functional Food - Improve Health through Adequate Food"},signatures:"Yvonne Maphosa and Victoria A. Jideani",authors:[{id:"201151",title:"Ph.D. Student",name:"Yvonne",middleName:null,surname:"Maphosa",slug:"yvonne-maphosa",fullName:"Yvonne Maphosa"}]}],onlineFirstChaptersFilter:{topicId:"200",limit:6,offset:0},onlineFirstChaptersCollection:[{id:"82616",title:"The Quantum Theory of Reproduction – How Unique is an Individual?",slug:"the-quantum-theory-of-reproduction-how-unique-is-an-individual",totalDownloads:12,totalDimensionsCites:0,doi:"10.5772/intechopen.105769",abstract:"Our understanding of nature’s way is founded on quantum mechanics. In its existence of over 80 years, quantum theory has been describing the physical world. The attraction of studying quantum mechanics is the perception of the conceptual structure of nature. This is aided by the mathematical structure that exposes the internal logic of the subject by inventing a notation that embeds the philosophy of the question. To describe how unique each individual is. A calculation method was applied. The uniqueness of an individual is one in two nonillion, octillion, septillion, sextillion, quintillion, quadrillion, trillion, billion, million and thousand. Individuals are indefinitely unique.",book:{id:"11284",title:"Studies in Family Planning",coverURL:"https://cdn.intechopen.com/books/images_new/11284.jpg"},signatures:"Zouhair O. Amarin"},{id:"81930",title:"Smoking and Its Consequences on Male and Female Reproductive Health",slug:"smoking-and-its-consequences-on-male-and-female-reproductive-health",totalDownloads:14,totalDimensionsCites:0,doi:"10.5772/intechopen.104941",abstract:"Smoking contributes to the death of around one in 10 adults worldwide. Specifically, cigarettes are known to contain around 4000 toxins and chemicals that are hazardous in nature. The negative effects of smoking on human health and interest in smoking-related diseases have a long history. Among these concerns are the harmful effects of smoking on reproductive health. Thirteen percent of female infertility is due to smoking. Female smoking can lead to gamete mutagenesis, early loss of reproductive function, and thus advance the time to menopause. It has been also associated with ectopic pregnancy and spontaneous abortion. Even when it comes to assisted reproductive technologies cycles, smokers require more cycles, almost double the number of cycles needed to conceive as non-smokers. Male smoking is shown to be correlated with poorer semen parameters and sperm DNA fragmentation. Not only active smokers but also passive smokers, when excessively exposed to smoking, can have reproductive problems comparable to those seen in smokers. In this book chapter, we will approach the effect of tobacco, especially tobacco smoking, on male and female reproductive health. This aims to take a preventive approach to infertility by discouraging smoking and helping to eliminate exposure to tobacco smoke in both women and men.",book:{id:"11284",title:"Studies in Family Planning",coverURL:"https://cdn.intechopen.com/books/images_new/11284.jpg"},signatures:"Amor Houda, Jankowski Peter Michael, Micu Romeo and Hammadeh Mohamad Eid"},{id:"81468",title:"The Knowledge and Use of Intra-Uterine Device by Women Attending Ante-Natal Clinic at Enugu State Teaching Hospital, Parklane",slug:"the-knowledge-and-use-of-intra-uterine-device-by-women-attending-ante-natal-clinic-at-enugu-state-te",totalDownloads:24,totalDimensionsCites:0,doi:"10.5772/intechopen.104097",abstract:"Intrauterine contraception has been recognized globally as one of the modern long-term reversible contraceptive methods suitable for women of all reproductive ages. It represents the most cost-effective method for preventing unwanted pregnancies, scientifically proven for its safety, efficacy and cost-effectiveness and is known to last longer in preventing pregnancy than other methods. This study assessed the knowledge of mothers attending ESUT teaching hospital, Parklane on intrauterine contraceptive device, the use as well as the common side effects experienced by the users. A descriptive survey research design was used to sample 175 mothers. A structured researcher developed questionnaire was used for data collection. The findings revealed that more than half of the respondents have good knowledge of intrauterine device but only 23 (14%) respondents make use of it. The commonly experienced side effects identified were irregular bleeding (75%) and vaginal discharge (62.5%). Although, the respondents had good knowledge of intrauterine device, their uptake of the method was poor. Therefore, there is a need to improve contraceptive counseling to ensure that women understand the relative effectiveness of IUDS. The study also recommended the need for better education for both clients and providers to improve the accessibility and acceptability of intrauterine device.",book:{id:"11284",title:"Studies in Family Planning",coverURL:"https://cdn.intechopen.com/books/images_new/11284.jpg"},signatures:"Chukwuasokam Caleb Aniechi and Uloma Cynthia Ezuma"},{id:"81003",title:"Perspective Chapter: Modern Birth Control Methods",slug:"perspective-chapter-modern-birth-control-methods",totalDownloads:42,totalDimensionsCites:0,doi:"10.5772/intechopen.103858",abstract:"This chapter focuses on various modern birth control methods, including combined oral contraceptives, progestogen-only pills, progestogen-only injectables, progestogen-only implants, intrauterine devices, barrier contraceptives, and emergency contraceptive pills. Each contraceptive method is covered in detail, including mechanism of action, effectiveness, health benefits, advantages, disadvantages, risks, and side-effects.",book:{id:"11284",title:"Studies in Family Planning",coverURL:"https://cdn.intechopen.com/books/images_new/11284.jpg"},signatures:"Rahma Al Kindi, Asma Al Salmani, Rahma Al Hadhrami, Sanaa Al Sumri and Hana Al Sumri"},{id:"80084",title:"Contraceptive Implants",slug:"contraceptive-implants",totalDownloads:174,totalDimensionsCites:0,doi:"10.5772/intechopen.101999",abstract:"Contraceptive implants or implantable contraceptive are five subdermal implants, rods the size of pencil lead that are embedded just under the skin on the inside of the upper arm. The rods contain etonogestrel, the metabolite of desogestrel, an equivalent progestin. Implants are often used during breastfeeding without an impact on milk production. It was identified that age does not affect the use of contraceptive implants but educational status is significant to its usage; there is an association between the age at first birth and the use of contraceptive implants; the number of liveborn children has a significant impact or influence on the use of implants; etc. This chapter focuses on types of contraceptive implants and its mechanism of action; global statistics on contraceptive implants; side effects; health benefits and positive characteristics of contraceptive implants; those who can and cannot use contraceptive implants; reasons women are not interested in contraceptive implants and factors influencing its usage.",book:{id:"11284",title:"Studies in Family Planning",coverURL:"https://cdn.intechopen.com/books/images_new/11284.jpg"},signatures:"Paul Hassan Ilegbusi"}],onlineFirstChaptersTotal:5},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:90,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:108,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:33,numberOfPublishedChapters:330,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:14,numberOfPublishedChapters:145,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:9,numberOfPublishedChapters:140,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:123,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:112,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:22,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:11,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:"2753-6580",doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}},{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}}]},series:{item:{id:"11",title:"Biochemistry",doi:"10.5772/intechopen.72877",issn:"2632-0983",scope:"Biochemistry, the study of chemical transformations occurring within living organisms, impacts all areas of life sciences, from molecular crystallography and genetics to ecology, medicine, and population biology. Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. This Biochemistry Series will address the current research on biomolecules and the emerging trends with great promise.",coverUrl:"https://cdn.intechopen.com/series/covers/11.jpg",latestPublicationDate:"August 2nd, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:33,editor:{id:"31610",title:"Dr.",name:"Miroslav",middleName:null,surname:"Blumenberg",slug:"miroslav-blumenberg",fullName:"Miroslav Blumenberg",profilePictureURL:"https://mts.intechopen.com/storage/users/31610/images/system/31610.jpg",biography:"Miroslav Blumenberg, Ph.D., was born in Subotica and received his BSc in Belgrade, Yugoslavia. He completed his Ph.D. at MIT in Organic Chemistry; he followed up his Ph.D. with two postdoctoral study periods at Stanford University. Since 1983, he has been a faculty member of the RO Perelman Department of Dermatology, NYU School of Medicine, where he is codirector of a training grant in cutaneous biology. Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. He has published more than 100 peer-reviewed research articles and graduated numerous Ph.D. and postdoctoral students.",institutionString:null,institution:{name:"New York University Langone Medical Center",institutionURL:null,country:{name:"United States of America"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:4,paginationItems:[{id:"14",title:"Cell and Molecular Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/14.jpg",isOpenForSubmission:!0,editor:{id:"165627",title:"Dr.",name:"Rosa María",middleName:null,surname:"Martínez-Espinosa",slug:"rosa-maria-martinez-espinosa",fullName:"Rosa María Martínez-Espinosa",profilePictureURL:"https://mts.intechopen.com/storage/users/165627/images/system/165627.jpeg",biography:"Dr. Rosa María Martínez-Espinosa has been a Spanish Full Professor since 2020 (Biochemistry and Molecular Biology) and is currently Vice-President of International Relations and Cooperation development and leader of the research group 'Applied Biochemistry” (University of Alicante, Spain). Other positions she has held at the university include Vice-Dean of Master Programs, Vice-Dean of the Degree in Biology and Vice-Dean for Mobility and Enterprise and Engagement at the Faculty of Science (University of Alicante). She received her Bachelor in Biology in 1998 (University of Alicante) and her PhD in 2003 (Biochemistry, University of Alicante). She undertook post-doctoral research at the University of East Anglia (Norwich, U.K. 2004-2005; 2007-2008).\nHer multidisciplinary research focuses on investigating archaea and their potential applications in biotechnology. She has an H-index of 21. She has authored one patent and has published more than 70 indexed papers and around 60 book chapters.\nShe has contributed to more than 150 national and international meetings during the last 15 years. Her research interests include archaea metabolism, enzymes purification and characterization, gene regulation, carotenoids and bioplastics production, antioxidant\ncompounds, waste water treatments, and brines bioremediation.\nRosa María’s other roles include editorial board member for several journals related\nto biochemistry, reviewer for more than 60 journals (biochemistry, molecular biology, biotechnology, chemistry and microbiology) and president of several organizing committees in international meetings related to the N-cycle or respiratory processes.",institutionString:null,institution:{name:"University of Alicante",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"15",title:"Chemical Biology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",isOpenForSubmission:!0,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. He studied at Stetson University, USA, in 2007-2008 and at the Max Planck Institute of Molecular Cell Biology and Genetics, Germany, in 2009-2010. Dr. Ekinci currently works as a Full Professor of Biochemistry in the Faculty of Agriculture and is the Head of the Enzyme and Microbial Biotechnology Division, Ondokuz Mayıs University, Turkey. He is a member of the Turkish Biochemical Society, American Chemical Society, and German Genetics society. Dr. Ekinci published around ninety scientific papers, reviews and book chapters, and presented several conferences to scientists. He has received numerous publication awards from several scientific councils. Dr. Ekinci serves as the Editor in Chief of four international books and is involved in the Editorial Board of several international journals.",institutionString:null,institution:{name:"Ondokuz Mayıs University",institutionURL:null,country:{name:"Turkey"}}},editorThree:null},{id:"17",title:"Metabolism",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",isOpenForSubmission:!0,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. His teaching areas are energy metabolism and regulation, integration and organ specialization and metabolic adaptation.",institutionString:null,institution:{name:"Artois University",institutionURL:null,country:{name:"France"}}},editorTwo:null,editorThree:null},{id:"18",title:"Proteomics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/18.jpg",isOpenForSubmission:!0,editor:{id:"200689",title:"Prof.",name:"Paolo",middleName:null,surname:"Iadarola",slug:"paolo-iadarola",fullName:"Paolo Iadarola",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bSCl8QAG/Profile_Picture_1623568118342",biography:"Paolo Iadarola graduated with a degree in Chemistry from the University of Pavia (Italy) in July 1972. He then worked as an Assistant Professor at the Faculty of Science of the same University until 1984. In 1985, Prof. Iadarola became Associate Professor at the Department of Biology and Biotechnologies of the University of Pavia and retired in October 2017. Since then, he has been working as an Adjunct Professor in the same Department at the University of Pavia. His research activity during the first years was primarily focused on the purification and structural characterization of enzymes from animal and plant sources. During this period, Prof. Iadarola familiarized himself with the conventional techniques used in column chromatography, spectrophotometry, manual Edman degradation, and electrophoresis). Since 1995, he has been working on: i) the determination in biological fluids (serum, urine, bronchoalveolar lavage, sputum) of proteolytic activities involved in the degradation processes of connective tissue matrix, and ii) on the identification of biological markers of lung diseases. In this context, he has developed and validated new methodologies (e.g., Capillary Electrophoresis coupled to Laser-Induced Fluorescence, CE-LIF) whose application enabled him to determine both the amounts of biochemical markers (Desmosines) in urine/serum of patients affected by Chronic Obstructive Pulmonary Disease (COPD) and the activity of proteolytic enzymes (Human Neutrophil Elastase, Cathepsin G, Pseudomonas aeruginosa elastase) in sputa of these patients. More recently, Prof. Iadarola was involved in developing techniques such as two-dimensional electrophoresis coupled to liquid chromatography/mass spectrometry (2DE-LC/MS) for the proteomic analysis of biological fluids aimed at the identification of potential biomarkers of different lung diseases. He is the author of about 150 publications (According to Scopus: H-Index: 23; Total citations: 1568- According to WOS: H-Index: 20; Total Citations: 1296) of peer-reviewed international journals. He is a Consultant Reviewer for several journals, including the Journal of Chromatography A, Journal of Chromatography B, Plos ONE, Proteomes, International Journal of Molecular Science, Biotech, Electrophoresis, and others. He is also Associate Editor of Biotech.",institutionString:null,institution:{name:"University of Pavia",institutionURL:null,country:{name:"Italy"}}},editorTwo:{id:"201414",title:"Dr.",name:"Simona",middleName:null,surname:"Viglio",slug:"simona-viglio",fullName:"Simona Viglio",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRKDHQA4/Profile_Picture_1630402531487",biography:"Simona Viglio is an Associate Professor of Biochemistry at the Department of Molecular Medicine at the University of Pavia. She has been working since 1995 on the determination of proteolytic enzymes involved in the degradation process of connective tissue matrix and on the identification of biological markers of lung diseases. She gained considerable experience in developing and validating new methodologies whose applications allowed her to determine both the amount of biomarkers (Desmosine and Isodesmosine) in the urine of patients affected by COPD, and the activity of proteolytic enzymes (HNE, Cathepsin G, Pseudomonas aeruginosa elastase) in the sputa of these patients. Simona Viglio was also involved in research dealing with the supplementation of amino acids in patients with brain injury and chronic heart failure. She is presently engaged in the development of 2-DE and LC-MS techniques for the study of proteomics in biological fluids. The aim of this research is the identification of potential biomarkers of lung diseases. 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Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:"Shenzhen Technology University",institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda R.",middleName:"R.",surname:"Gharieb",fullName:"Reda R. Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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