Microbacterium diet rich in branched chain fatty acids promotes lipid droplet enlargement and impacts organismal health in C. elegans

Considerable amounts of branched chain fatty acids (BCFAs) are present in the human diet from beef and dairy products. BCFAs can also be produced by the human gut microbiota and synthesized from branched chain amino acids. However, the physiological impact of a BCFA-rich diet on lipid metabolism and organismal health is unclear. In this study, by screening a collection of dietary bacteria, we find that the BCFA-rich Microbacterium diet causes the formation of supersized LDs and delays development, reduces brood size, and shortens the lifespan of Caenorhabditis elegans. The high-BCFA diet downregulates argk-1/creatine kinase to inhibit the AMPK pathway and β-oxidation and upregulates fat-7/desaturase to promote the accumulation of PUFAs, which enhances lipogenesis and LD expansion. We also isolate a gain-of-function mutation in scav-4/CD36, which enhances BCFA absorption and exacerbates BCFA-induced LD enlargement, demonstrating that host genetic variation in a fatty acid transporter could influence the susceptibility to a high-BCFA diet.