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

Nature Metabolism
Shannon M ReillyAlan R Saltiel

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.

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Citations

Mar 7, 2021·Metabolites·Helaina Von BankJudith Simcox
Jul 24, 2021·Frontiers in Physiology·M Brennan Harris, Chia-Hua Kuo

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Methods Mentioned

BETA
confocal microscopy
PCR
electron microscopy
immunoprecipitation
electrophoresis
co-immunoprecipitation
ELISA
nuclear magnetic resonance
Profiler
transfection

Software Mentioned

GraphPad
Volocity
Cuffdiff
Prism
EchoMRI
CummeRbund
TopHat2

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