The interaction between obesity, immune response, and T cell metabolism
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Obesity is the result of positive energy balance over a long period of time. Current research suggests that obesity is a multifactorial phenotype resulting from a combination of several factors, including genetic, epigenetic, sedentary behavior and dietary macronutrient composition. The major consequences of obesity include dyslipidemia, hyperglycemia, insulin resistance, altered adipokines, and altered immune function. Obesity increases fat deposition in tissues of the immune system such as bone marrow and thymus. Ectopic lipid metabolites change the individual immune cell profiles. In inflamed adipose tissues, anti-inflammatory M2 macrophages shift toward the M1 pro-inflammatory phenotype. The increase in CD8⁺ T cells precedes the accumulation of macrophages. Th1 and CD8⁺ T cells promote the development of insulin resistance (IR), while T-reg cells inhibit IR. The activation of naïve T cells is an energy-demanding activity that requires metabolic reprogramming. Proliferating cells switch to anabolic metabolism from catabolic metabolism, and nutrient substrates are utilized for biosynthesis of new daughter cells. Differentiated T effector cells, such as Th1/Th2, Th17 and Treg, display a more elevated rate of glycolysis than naïve T cells. Notably, Treg has the least glycolytic metabolism but an elevated rate of lipid oxidation. Naïve T cells utilize glucose and glutamine at a relatively low rate to maintain normal housekeeping functions, such as ion transport and membrane integrity. Resting T cells rely on oxidative phosphorylation for ATP production. Glutamine provides energy via oxidative metabolism and supports the biosynthetic processes by providing carbon and nitrogen precursors. In activated T cells, glucose-6-phosphate can enter the pentose phosphate pathway for the production of 5-carbon sugars for nucleotide biosynthesis and NADPH. Additionally, the TCA cycle can also serve as a center of biosynthesis in addition to providing proton carriers that facilitate in the generation of ATP from glucose in naïve T cells. In conclusion, obesity causes chronic inflammation that alters the immune cells profiles, particularly, T cells. Furthermore, T cell metabolism is also altered by the exposure to the major consequences of obesity, hyperlipidemia and hyperglycemia, shifting T cell population into Th17 subsets.