Targeting obesity-related inflammation through nutritional and genetic approaches

Date

2015-08

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Abstract

Over one-third of adults in America suffer from obesity, a disease that is associated with the over-expansion of adipose tissue, along with increases in blood pressure, glycemia, inflammation and thrombosis. Low-grade chronic inflammation has been causally linked with obesity, though the mechanisms involved are not clear. Therefore for this dissertation, we were interested in developing genetic and nutritional approaches that could be used to target obesity-induced inflammation and dissect potential mechanisms involved. Specifically, we determined the role of the renin-angiotensin system (RAS) and the protective benefits of the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid (EPA), on adipose tissue dysfunction and inflammation. We demonstrated in this work that inactivation of angiotensinogen (Agt) specifically in adipose tissue reduced features of obesity-induced inflammation including total macrophage infiltration, and pro-inflammatory cytokine production while increasing metabolic activity. We also showed that EPA ameliorated high-fat diet effects at least in part by increasing oxygen consumption and fatty acid oxidation, reducing adipocyte size, adipogenesis and adipose tissue inflammation, independent of obesity. In conclusion, our findings indicate that EPA feeding and inactivation of Agt could be used as a potential means to reduce inflammation locally in adipose tissue. Both approaches provided insight into potential mechanisms involved in obesity-associated insulin resistance and inflammation and may prove valuable for future clinical studies using nutritional/ pharmacological therapies against obesity and other inflammatory metabolic disorders.

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Keywords

Obesity, Renin-Angiotensingon System, Omega-3 Fatty Acids, Inflammation

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