Ngoc-Anh Le

By Ngoc-Anh Le

Among the most common non-communicable diseases are obesity, cardiovascular disease, and diabetes, which are responsible for the major cardiometabolic phenotypes. Together with mitochondrial alterations, oxidative stress and inflammation are key molecular mechanisms that contribute to the onset and development of these conditions. Meal consumption is a recurring daily activity that is directly linked to oxidative stress and inflammation. Acute increases in lipids, notably triglycerides, during the postabsorptive period have been suggested to induce a state of inflammation with stimulation of adhesion molecules, cytokines, oxidative stress, and leukocyte activation. Not only lipids but also meal-induced elevations in glucose have also been linked to postprandial oxidative stress and inflammation. The impact of postprandial hypertriglyceridemia and hyperglycemia on oxidative stress and inflammation is not only independent but may be cumulative. It is our hypothesis that, in a system that could not maintain homeostasis to continuous changes of the environment, repeated exposures to meals that provide modest doses of fat and glucose could potentially elicit abnormal responses that contribute to the onset and development of chronic cardiometabolic phenotypes.

Part of the book: Apolipoproteins, Triglycerides and Cholesterol

By Ngoc-Anh Le

As inflammatory and oxidative stress are associated with cardiometabolic diseases, detection of abnormal fasting levels of inflammatory and oxidative biomarkers are indicative disease presence and may be too late for any preventive management. Metabolic flexibility refers to the ability of various metabolic processes to compensate for these acute changes and return all metabolites to baseline levels. By monitoring responses of key biomarkers to a standardized physiologic challenge, it is possible to assess the ability of the body to restore homeostasis, that is a measure of metabolic flexibility. Acute changes in lipoprotein-associated biomarkers of oxidative stress have been demonstrated following meal consumption. These include changes in circulating levels of oxidized low-density lipoproteins (LDL), levels of autoantibodies to malondialdehyde-modified LDL, as well as the oxidative susceptibility of isolated plasma LDL. These responses depend on the type and amount of dietary fats in the meal. Management with certain lipid-lowering drugs could also be shown to affect these meal-induced changes. However, plasma levels may be underestimated as we can demonstrate a spike in lipoprotein-associated biomarkers of oxidative stress resulting from the release oxidatively modified epitopes from the arterial wall by an intravenous bolus of heparin.

Part of the book: Importance of Oxidative Stress and Antioxidant System in Health and Disease

By Ngoc-Anh Le

Many commonly known antioxidants, from probucol to vitamin E, are fat-soluble and have been shown to be most effective when administered with meals. Following meal consumption, these compounds are incorporated into intestinal lipoproteins, known as chylomicrons, and secreted into the circulation. These lipid-carrying particles are responsible for the transport of newly absorbed dietary fat for delivery to peripheral tissues. In the bloodstream, chylomicrons interact with heparin-releasable lipases common known as lipoprotein lipase and hepatic triglyceride lipase. Bothe lipases are anchored along the endothelial wall via heparan sulfate proteoglycans and have triglycerides as their preferred substrate. During this process, as dietary triglycerides are hydrolyzed and transported across the endothelium, we hypothesize that antioxidants carried in chylomicrons would be delivered directly to the arterial wall where they would be most effective in quenching reactive oxygen species generated by activated macrophages. Thus, the metabolism of postprandial lipoproteins is a key process in the defense against oxidative stress and may provide the path for effective antioxidant management. In this chapter, we will review the evidence in support of the hypothesis that postprandial lipoproteins may contribute to the delivery of fat-soluble antioxidants that are administered orally.

Part of the book: The Power of Antioxidants - Unleashing Nature's Defense Against Oxidative Stress [Working title]