Catecholamines suppress fatty acid re-esterification and increase oxidation in white adipocytes via STAT3

Nat Metab. 2020 Jul;2(7):620-634. doi: 10.1038/s42255-020-0217-6. Epub 2020 Jun 8.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, White / metabolism*
  • Adrenergic beta-Agonists / pharmacology
  • Animals
  • Catecholamines / pharmacology*
  • Diet, High-Fat
  • Energy Metabolism
  • Esters / metabolism
  • Fatty Acids, Nonesterified / metabolism*
  • Lipolysis
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Obesity / metabolism
  • Oxidation-Reduction
  • Phosphorylation
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*

Substances

  • Adrenergic beta-Agonists
  • Catecholamines
  • Esters
  • Fatty Acids, Nonesterified
  • STAT3 Transcription Factor
  • Stat3 protein, mouse