Mechanisms mediating anti inflammatory effects of omega 3 fatty acids in metabolic disorders: role of lipid mediators and micro RNAs

Abstract

Obesity is a complex disease that increase mortality and co-morbid diseases such as diabetes and cardiovascular diseases, and is characterized by adipose tissue expansion and inflammation. Recent studies shows that lipid mediators (leukotrienes LTB4 and platelet activating factor PAF) are responsible for chronic inflammation which in turn leads to obesity and insulin resistence. Long-chain omega-3 polyunsaturated fatty acid (PUFA) from fish oil are potent anti-inflammatory nutrients that are known to reduce the levels of prostaglandin E2, LTB4 and other inflammatory markers. Interestingly, LTB4 controls the profile of miRNA expression and modulates the inflammatory response in innate immunity cells such as macrophages. Adipose inflammation is primarily mediated by microphages that infiltrate the fat tissue. However, the role of omega-3s in regulating lipid mediators to prevent or treat chronic inflammation is currently unknown. Hence, we hypothesize that fish oil will lower the chronic low grade inflammation associated with metabolic dysfunctions by reducing adiposity and insulin resistance. We further lypothesize that these effects are mediated by mechanisms which involve lipid mediators such as LTB4 and PAF and regularory miRNAs. This hypotesis will be tested in three specific aims through a series of integrated cellular, molecular and physiological studies using mouse models and adipose cell cultures. Importantly the foundation for the proposed research is based on strong established and complementary expertise and published work by the TTU (obesity / adipose tissue) and USP (immunology) partnering teams. (AU)