Monomethyl Branched Chain Fatty Acids link Mitochondrial Amino Acid Metabolism and Adipose Tissue Lipogenesis to Fatty Acid Diversity

Abstract

BCAA's are important substrates for protein synthesis and bioenergetics in mammals, and this metabolic pathway is dysregulated in various disease states. Fatty acid biosynthesis occurs in many tissues, but the balance of lipogenesis in liver and adipose tissue is disturbed in the context of obesity and metabolic syndrome. Here, using in vitro and in vivo stable isotope tracing we demonstrate that these pathways are linked within adipose tissue, where mammalian FAS produces monomethyl branched chain fatty acids (mmBCFAs). BCAA catabolic flux and short chain fatty acids from the gut microbiome initiate fatty acid synthesis in brown and beige adipocytes to influence the diversity of fatty acids present in the body. Diet‐induced obesity decreases BCAA catabolism and adipose tissue de novo lipogenesis such that mmBCFAs are the most reduced fatty acid species detected and mmBCFA abundance correlates negatively with markers of non‐alcoholic steatohepatitis. These results highlight the origin and regulation of mmBCFAs in mammals, which may play functional roles in metabolic homeostasis, nutrient sensing, and membrane function in human disease.Support or Funding InformationAjinomoto Innovation Alliance Program Grant.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.