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

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.
Shannon M Reilly 1 2,  Chao-Wei Hung 3,  Maryam Ahmadian 3 4,  Peng Zhao 3 5,  Omer Keinan 3,  Andrew V Gomez 3,  Julia H DeLuca 3,  Benyamin Dadpey 3,  Donald Lu 3,  Jessica Zaid 3,  BreAnne Poirier 5 6,  Xiaoling Peng 5,  Ruth T Yu 4,  Michael Downes 4,  Christopher Liddle 4,  Ronald M Evans 4,  Anne N Murphy 7 8,  Alan R Saltiel 9 10 11
Affiliations

Affiliations

  • 1 Division of Metabolism and Endocrinology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA. shreilly@ucsd.edu.
  • 2 Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA. shreilly@ucsd.edu.
  • 3 Division of Metabolism and Endocrinology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • 4 Gene Expression Laboratory, Salk Institute for Biological Sciences, La Jolla, CA, USA.
  • 5 Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA.
  • 6 Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
  • 7 Department of Pharmacology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
  • 8 Cytokinetics, South San Francisco, CA, USA.
  • 9 Division of Metabolism and Endocrinology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA. asaltiel@ucsd.edu.
  • 10 Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA. asaltiel@ucsd.edu.
  • 11 Department of Pharmacology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA. asaltiel@ucsd.edu.
PMID: 32694788 DOI: 10.1038/s42255-020-0217-6
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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