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
  • 1. Division of Metabolism and Endocrinology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA. [email protected].
  • 2. Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA. [email protected].
  • 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. [email protected].
  • 10. Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA. [email protected].
  • 11. Department of Pharmacology, Department of Medicine, University of California, San Diego, La Jolla, CA, USA. [email protected].
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.

Products