Mus musculus Transcriptome or Gene expression

Catecholamines stimulate the mobilization of stored triglycerides in adipocytes to provide fatty acids (FAs) for other tissues. However, a large proportion is taken back up and either oxidized or re-esterified. What controls the disposition of these FAs in adipocytes remains unknown. Here we report that catecholamines redirect fatty acids for oxidation through the phosphorylation of a specific pool of signal transducer and activator of transcription 3 (STAT3). Upon activation of ß-adrenergic receptors, STAT3 is phosphorylated and subsequently binds to and inhibits glycerol-3-phosphate acyltransferase 3 (GPAT3), effectively suppressing fatty acid re-esterification, to promote oxidation. Adipocyte-specific Stat3 KO mice exhibit normal rates of lipolysis, but manifest a specific defect in lipolysis-driven oxidative metabolism, resulting in reduced energy expenditure and increased adiposity on high fat diet. This previously unappreciated, non-genomic role of STAT3 explains how sympathetic activation can increase both lipolysis and fatty acid oxidation in adipocytes, revealing a new regulatory axis in metabolism.