Glycogen metabolism links glucose homeostasis to thermogenesis in adipocytes

Nature. 2021 Nov;599(7884):296-301. doi: 10.1038/s41586-021-04019-8. Epub 2021 Oct 27.

Abstract

Adipocytes increase energy expenditure in response to prolonged sympathetic activation via persistent expression of uncoupling protein 1 (UCP1)1,2. Here we report that the regulation of glycogen metabolism by catecholamines is critical for UCP1 expression. Chronic β-adrenergic activation leads to increased glycogen accumulation in adipocytes expressing UCP1. Adipocyte-specific deletion of a scaffolding protein, protein targeting to glycogen (PTG), reduces glycogen levels in beige adipocytes, attenuating UCP1 expression and responsiveness to cold or β-adrenergic receptor-stimulated weight loss in obese mice. Unexpectedly, we observed that glycogen synthesis and degradation are increased in response to catecholamines, and that glycogen turnover is required to produce reactive oxygen species leading to the activation of p38 MAPK, which drives UCP1 expression. Thus, glycogen has a key regulatory role in adipocytes, linking glucose metabolism to thermogenesis.

Publication types

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

MeSH terms

  • Adaptation, Physiological
  • Adipocytes / metabolism*
  • Adipocytes, Beige / metabolism
  • Animals
  • Cold Temperature
  • Energy Metabolism
  • Female
  • Glucose / metabolism*
  • Glycogen / metabolism*
  • Homeostasis*
  • Humans
  • Intracellular Signaling Peptides and Proteins / deficiency
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Thermogenesis*
  • Uncoupling Protein 1 / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Intracellular Signaling Peptides and Proteins
  • Ppp1r3c protein, mouse
  • Ucp1 protein, mouse
  • Uncoupling Protein 1
  • Glycogen
  • p38 Mitogen-Activated Protein Kinases
  • Glucose