De novo Lipogenesis in Adipocytes Results in the Production of Structurally Novel Signaling Lipids with Beneficial Metabolic and Anti‐inflammatory Effects

Abstract

Increased de novo lipogenesis in adipose tissue is associated with enhanced insulin sensitivity in humans and rodents. Mice overexpressing the Glut4 glucose transporter in adipose tissue have elevated adipose tissue lipogenesis and increased glucose tolerance in spite of obesity and elevated circulating fatty acids. Untargeted lipidomic analysis of adipose tissue from these mice revealed marked elevation of a structurally novel class of lipids, branched Fatty Acid esters of Hydroxy Fatty Acids (FAHFAs). More than 25 FAHFA family members, which are distinguished by different acyl chain composition, have been identified in mammalian tissues and plants. Levels of some family members such as Palmitic Acid esters of Hydroxy Stearic Acids (PAHSAs) are highly regulated in altered nutritional and metabolic states. PAHSA levels are reduced in serum and subcutaneous adipose tissue of insulin‐resistant humans and serum PAHSA levels correlate very strongly with insulin sensitivity in humans. Chronic PAHSA treatment improves glucose tolerance and insulin sensitivity in insulin‐resistant mice. PAHSAs also have anti‐inflammatory effects in states such as obesity, colitis and auto‐immune Type 1 diabetes in mice. Many effects of PAHSA are mediated through G‐protein coupled receptors. Thus, PAHSAs exert multiple beneficial metabolic and anti‐inflammatory effects in diabetes and immune‐mediated diseases. The pathways that regulate these lipids provide new opportunities for disease prevention and treatment.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.