Open AccessCatecholamines suppress fatty acid re-esterification and increase oxidation in white adipocytes via STAT3
Author(s) -
Shan M. Reilly,
ChaoWei Hung,
Maryam Ahmadian,
Peng Zhao,
Omer Keinan,
Andrew V. Gomez,
Julia H DeLuca,
Benyamin Dadpey,
Donald Lu,
Jessica Zaid,
BreAnne Poirier,
Xiaoling Peng,
Ruth T. Yu,
Michael Downes,
Christopher Liddle,
Ronald M. Evans,
Anne N. Murphy,
Alan R. Saltiel
Publication year - 2020
Publication title -
nature metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.834
H-Index - 22
ISSN - 2522-5812
DOI - 10.1038/s42255-020-0217-6
Subject(s) - lipolysis , adipocyte , medicine , chemistry , endocrinology , beta oxidation , stat3 , phosphorylation , oxidative phosphorylation , fatty acid , stat protein , white adipose tissue , adipose tissue , biochemistry , biology
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 FAs for oxidation through the phosphorylation of signal transducer and activator of transcription 3 (STAT3). Adipocyte STAT3 is phosphorylated upon activation of β-adrenergic receptors, and in turn suppresses FA re-esterification to promote FA oxidation. Adipocyte-specific Stat3 KO mice exhibit normal rates of lipolysis, but exhibit defective lipolysis-driven oxidative metabolism, resulting in reduced energy expenditure and increased adiposity when they are on a high-fat diet. This previously unappreciated, non-genomic role of STAT3 explains how sympathetic activation can increase both lipolysis and FA oxidation in adipocytes, revealing a new regulatory axis in metabolism.