Mechanism and Impact of Food Components in Burning Calories from White-to-Brown Adipose Tissue

Abstract

Obesity is one of the nutritional public health concerns of today’s world. It is defined as the abnormal accumulation of fat as a result of positive energy balance in the body. As the trend of overweight and obesity is increasing at the fastest pace affecting both children and adults; so, a search of new therapeutic guidelines is required to ameliorate the status of weight gain. Various researches are carried on regarding the activation of brown adipose tissue (BAT) for amplifying energy expenditure (EE) through heat production. Browning of white adipose tissue (WAT), now-a-days gained more attention and is considered as another tool for stimulating calorie burning. This chapter portrays the recent knowledge of some food ingredients that can enhance activation of BAT and browning of WAT with their beneficial health consequences.

1. Introduction

Overweight and Obesity is considered as the main chauffeur for an umbrella of diseases like type 2 diabetes mellitus, insulin resistance (IR), non-alcoholic fatty liver, hypertension, dyslipidemia, heart diseases, orthopedic disorders, asthma, hormonal imbalances, several types of cancers, disability, and many other types of diseases. The fundamental causes of overweight and obesity are a result of positive energy balance between energy intake and its expenditure or a combination of both. The World Health Organization (WHO) has reported that obesity more than 1.9 billion adults were overweight; of these over 650 million were obese in the year 2016. It was also reported by WHO in the year 2019 that 38.3 million children under 5 were overweight or obese [1]. There are an array of factors that leads to overweight and obesity which include age, gender, genetic predisposition, sedentary lifestyle, socio-economic status, faulty eating habits (processed and energy-dense foods), and so on.

Generally, weight management is focused on two modifications i.e., lifestyle modification and improving eating habits. It is well known that the principal depot for energy storage is WAT and on the contrary basis, BAT is responsible for thermogenic energy expenditure. BAT had a significant capacity to dissipate energy and regulate triglycerides and glucose metabolism; act as a potential target for the treatment of overweight and obesity as well as metabolic disorders [2].

2. Adipose tissues: origin and development

Adipose tissue is fundamentally fabricated from adipocytes as well as pre-adipocytes, macrophages, endothelial cells, fibroblasts, and leucocytes that are considered as a major player of systemically metabolic regulation [3]. The adipose tissue acts as a central metabolic organ for systematic energy homeostasis by acting as a caloric reservoir [4]. It is characterized as an important endocrine organ that is responsible for the secretion of many molecules like proteins, lipids and, miRNA (microRNA) [5]. These elements act as paracrine and endocrine signals that are critical for the function of adipose tissue as well as for non-adipose tissues that are required for the regulation of the body’s metabolism and insulin sensitivity [4, 5].

Broadly, adipocytes are classified into two main categories i.e., white or brown adipocytes depending upon their morphology and nature of work/function. Adipose tissues also act as endocrine organs that are responsible for the secretion of multiple hormones. WAT plays a role in fatty acid biosynthesis by storing lipids in form of triglycerides as its cell have large vacuoles and fewer mitochondria. Similarly, BAT plays a role in glucose uptake and fatty acid breakdown, leading to energy dissipation and heat production. Its cells are multilocular with central nuclei and mitochondria rich in the expression of uncoupling protein-1 (UCP-1) that mediates the uncoupling of electron transport that leads to a decrement in the generation of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) with subsequent heat generation [5, 6]. The principal function of BAT is non-shivering thermogenesis; an energy-intensive process in which chemical energy is transformed into physical heat [5]. Further, the process of thermogenesis is also performed by the third type of adipose tissue cell known as beige adipocytes. Beige adipocytes have many properties similar to brown adipocytes i.e., the presence of multilocular lipid droplets and numerous mitochondria expressing UCP-1 [5]. However, the process of thermogenesis is not restricted to brown adipocytes but it may be done by beige adipocytes that may emerge within WAT depots in a process known as “WAT browning” [5, 6, 7]. The physiological, morphological, cell composition, and function of adipocytes are shown in Figure 1.

Figure 1.

Physiological, morphological, cell composition, and function of adipocytes. The figure was modified from the following research paper by El Hadi et al., 2019.

3. Food components involved in browning of WAT

Numerous dietary factors are involved in the activation of BAT or browning of WAT via the main physiologic mechanism well shown in Figures 2 and 3.

Figure 2.

Food components involved in the induction of WAT browning. Here, PUFAs- polyunsaturated fatty acids, WAT- white adipose tissue, TRPM8- transient receptor potential cation channel melastatin 8, UCP1- uncoupling protein 1, TRPV1-transient receptor potential vanilloid 1, SNA- sympathetic nerve activity; AMPK- adenosine monophosphate-activated protein kinase, SIRT1- sirtuin-1, PGC-1α-peroxisome proliferator-activated receptor gamma coactivator 1-alpha, COMT- catechol-O-methyl-transferase, cAMP- cyclic adenosine monophosphate, PDEs- phosphodiesterases. The figure was modified from the following research paper by El Hadi et al., 2019. The images used in drawing the figure were extracted from the following links as described below: 1. PUFAs- Walnut- https://5.imimg.com/data5/JR/AK/VJ/SELLER-2793878/walnut-500x500.jpg, fish- https://www.bigbasket.com/media/uploads/p/xxl/40186851_1-fresho-atlantic-salmon.jpg, soyabean oil- https://image.shutterstock.com/image-photo/soybean-oil-bottle-green-pods-260nw-310996568.jpg, sunflower seeds- https://zonefresh.com.au/wp-content/uploads/SUNFLOWER-KERNELS.jpg, 2. Curcumin- https://5.imimg.com/data5/SELLER/Default/2020/9/VE/PK/ZA/24380440/curcumin-extract-500x500.jpg, 3. Resveratrol- https://news.mit.edu/sites/default/files/styles/news_article__image_gallery/public/images/201303/20130307093438-0_0.jpg?itok=xnIFxN6G, 4. Menthol- https://smhttp-ssl-61936.nexcesscdn.net/media/catalog/product/optimized/7/5/75ea61bf1685045cff4a80f864b6472f/flavor-west-natural-menthol.jpg, 5. Capsaicin/capsinoids- https://article.innovadatabase.com/articleimgs/article_images/flavors8.jpg, 6. Green tea- https://femina.wwmindia.com/content/2018/nov/thumbnail1541742051.jpg.

Figure 3.

Dietary components involved in the mechanism involved in brown adipogenesis, mitochondrial biogenesis, and energy expenditure. (a) Activation of SIRT1 either directly and/or indirectly through AMPK results in deacetylation and interaction of key transcription factors that induce brown and beige adipogenesis as PPAR α/γ and PRDM16. It was also found that PPAR/PRDM16 complex was able to bind and activate PGC1α, another co-factor expressed in brown and beige adipocytes that trigger the transcription of multiple genes engaged in thermogenesis and mitochondrial biogenesis. Likewise, AMPK may also directly magnify PGC1α activity by phosphorylation, which ultimately increases mitochondrial biogenesis. (b) The activation of TRPM8 in brown adipocytes increases the expression of thermogenic genes through the Ca2 + dependent PKA signaling pathway. (c) Due to the triggering of TRPV1 receptors in the gastrointestinal tract, and stimulation of the vagal afferent pathways, neurons within the ventromedial hypothalamus get activated. This leads to the induction of a cold-independent adrenergic response that intervenes brown adipogenesis. The adrenergic stimulation in brown adipocytes may also be promoted by decreasing the deterioration of (d) cAMP and (e) norepinephrine via direct inhibition of PDEs and COMT activity, respectively. Here, TRPM8-transient receptor potential cation channel melastatin 8, UCP1- uncoupling protein 1, TRPV1-transient receptor potential vanilloid 1, SNA- sympathetic nerve activity, AMPK- adenosine monophosphate-activated protein kinase, SIRT1- sirtuin-1, PGC-1α-peroxisome proliferator-activated receptor gamma coactivator 1-alpha, COMT- catechol-O-methyl-transferase, cAMP-cyclic adenosine monophosphate, PDEs- phosphodiesterases, PUFAs-polyunsaturated fatty acids, Ac-acetyl group, PPARα/γ peroxisome proliferator-activated receptor alpha/gamma, PKA- protein kinase A, PRDM16- PR-domain containing 16. (+) – stimulation, (−)- inhibition, increase. The figure was modified from the following research paper by El Hadi et al., 2019. The images used in drawing the figure were extracted from the following links as described below: 1. DNA- https://images.freeimg.net/thumbs/dna-2316536_1280.png, 2. Brain- https://timvandevall.com/wp-content/uploads/human-brain-parts-1.jpg, 3. Gastrointestinal tract- https://spng.subpng.com/20180425/fre/kisspng-gastrointestinal-tract-human-digestive-system-diag-abdominal-5ae0b2080064a3.8564190715246750800016.jpg.

3.1 Polyunsaturated fatty acids (PUFAs)

The major sources of PUFAs, mostly Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) are found in fatty fish such as salmon and anchovies as well as fish oil supplements [6]. Previous studies reported that EPA activates white adipocytes to beige-like adipocytes in overweight human subjects by stimulating the activation of the adenosine monophosphate-activated protein kinase (AMPK)/sirtuin-1 (SIRT1) /peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1- α axis) [6, 8]. Furthermore, many researchers also reported that fish oil contributes to brown adipogenesis by acting as a ligand of transient receptor potential vanilloid 1(TRPV1) in the digestive tract that triggers through the brain, a β 2-adrenergical sympathetic response in adipose depots [6].

3.2 Curcumin

Curcumin is the yellow-colored hydrophobic polyphenol that is available in extracts of turmeric roots belongs to the family of Zingiberaceae with genus Curcuma of the plant. It has numerous therapeutic potentials like anti-obesity, anti-diabetic, antioxidant, and anti-inflammatory; used as a spice in cooking generally in India. Akbari et al., 2019 stated that supplementation of curcumin decreases body mass index (BMI), percent body fat, leptin and increases adiponectin level in obese humans [9]. Earlier studies also reported that curcumin induces browning in WAT via adenosine monophosphate-activated protein kinase (AMPK) activation and inhibition of preadipocyte differentiation by downregulating the peroxisome proliferator-activated receptor gamma (PPAR γ) and CCCAAT/Enhancer Binding Protein α (C/EBP α) [5, 10, 11, 12].

3.3 Resveratrol

Resveratrol is a natural polyphenol that is mostly found in grapes (Vitaceae family with genus Vitis), blueberries (Ericaceae family with genus Vaccinium), cranberries (Ericaceae family with genus Vaccinium), red and white wines, peanuts (Fabaceae family with genus Arachis), cocoa and dark chocolates (Malvaceae family with genus Theobroma). It is well known that resveratrol plays numerous vital roles in the human body like anti-inflammatory as well as maintaining glucose metabolism and insulin sensitivity which are relevant to obesity [13]. It also possesses anti-lipolytic, cardioprotective, neuroprotective, and anti-cancerous effects [13]. Earlier studies revealed that resveratrol exerts thermogenic effects and contributes to increased respiration [14]. Another clinical study stated that resveratrol is considered a natural activator of the sirtuins family [15]. AMPK activation by resveratrol can stimulate mitochondrial biogenesis through SIRT1 [14]. Additionally, it also activates the deacetylation of PGC-1α, a regulator of energy metabolism that leads to ATP production by modulating mitochondrial function [13].

3.4 Menthol

Menthol is also called mint camphor that is produced from the plant peppermint (family Lamiaceae with genus Mentha) or maybe extracted synthetically. Menthol possesses various biological properties like anti-inflammatory, anti-bacterial, antipruritic, antitussive, and analgesic properties [6, 16]. Since menthol induces cooling sensation by activating the TRPM8 receptor, a Ca2 + − permeable non-selective channel that detects cold stimuli in the thermosensory system [6, 17, 18]. Several clinical studies also reported that menthol stimulates transient receptor potential cation channel melastatin 8 (TRPM8) expression on the white and brown adipocytes.

3.5 Capsaicin and Capsinoids

Capsaicin and capsinoids are the compounds that are generally found in red peppers belong to the family of Solanaceae with genus capsicum of the plant. Several studies reported that capsaicin and capsinoids have various properties like anti-obesity, anti-diabetic and anti-inflammatory. Earlier studies reported that capsaicin and capsinoids played a pivotal role in fat oxidation and EE [19]. Yoneshiro et al., 2013 reported that supplementation of capsinoids over 6 weeks decreases body weight in humans [20]. Despite the above, it was also reported that exposure of cold cumulative with ingestion of capsinoids results in activation of brown and beige adipose tissues [5, 20]. This activation happens as a result of activation of the transient receptor potential cation channel subfamily V member 1 (TRPV1) in the gastrointestinal tract which sends signals to the central nervous system (CNS) leading to 2-AR signaling activation in adipose tissue [5, 21]. It was also stated in earlier studies that capsaicin triggers browning of WAT by stimulating the expression of SIRT1, UCP1, bone morphogenetic protein 8B (BMP8B), and PPAR γ, PGC-1 α in white adipocytes.

3.6 Green tea

Green tea is considered a widely consumed beverage all over the world. It is extracted from fresh leaves of a green tea plant named Camellia sinensis belongs to the family of Theaceae. It contains huge amounts of polyphenols, mainly tea catechins like epicatechin, epicatechin gallate, and epigallocatechin that possesses properties like antioxidants, hypocholesterolemic, antihypertensive, and anticarcinogenic [14]. Various clinical studies also enumerated that consumption of green tea helps in weight management by modifying fat metabolism and calories expenditure. Earlier studies also reported that green tea contains a substantial amount of caffeine; which is known for its thermogenic properties [6, 22]. Dulloo et al., 1999 in human studies, also stated that green tea enhances fat oxidation and energy expenditure [23]. Nevertheless, catechins and caffeine may synergically mediate adrenergic-induced BAT thermogenesis by acting at different checkpoints of the norepinephrine-cyclic adenosine monophosphate (cAMP) axis. It was recommended that green tea catechins may promote sympathetic nerve activity (SNA) by decreasing the degradation of norepinephrine through direct inhibition of catechol-O-methyl-transferase (COMT) [6]. Furthermore, it was also reported that caffeine may synergically prolong the effects of norepinephrine by direct inhibition of phosphodiesterases (PDEs) activity [6, 23, 24].

4. Conclusion

Overweight and obesity are considered major risk factors for the number of non-communicable diseases like type 2 diabetes mellitus, non-alcoholic fatty liver, dyslipidemia, heart disease, some types of cancers, and many more. The main cause of overweight and obesity is increased fat mass; as all fat depots are not equally created. As we know that, adipocytes are present in WAT, contain large single fat droplets that act as a reservoir for energy storage. On the other hand, BAT play a specific role in thermoregulation. In this chapter, emphasis is given on some dietary components that have the potential to activate the regulation of BAT or beige fat development. Moreover, various clinical studies and trials showed that dietary components like PUFAs, curcumin, resveratrol, menthol, capsaicins/capsinoids, green tea, and many more when supplemented in adequate quantity show thermogenic effects. Therefore, further research is required to define and describe the methods by which these dietary components can be incorporated into the diet as well as about the bioavailability of these dietary components. Nevertheless, it can be stated that these dietary components may act as a boon in ameliorating the condition of overweight and obesity in the future.

Acknowledgments

A profound sense of gratitude to my beloved husband Mr. Nirmal Kumar for his love, understanding, opinion, encouragement, valuable suggestions, and useful comments throughout in writing this book chapter. I also apologize for not citing the research papers of all the authors that helped me in better understanding this topic.

Conflict of interest

The author declares no conflict of interest.