TGF-β2 is an exercise-induced adipokine that regulates glucose and fatty acid metabolism

Nat Metab. 2019 Feb;1(2):291-303. doi: 10.1038/s42255-018-0030-7. Epub 2019 Feb 11.

Abstract

Exercise improves health and well-being across diverse organ systems, and elucidating mechanisms underlying the beneficial effects of exercise can lead to new therapies. Here, we show that transforming growth factor-β2 (TGF-β2) is secreted from adipose tissue in response to exercise and improves glucose tolerance in mice. We identify TGF-β2 as an exercise-induced adipokine in a gene expression analysis of human subcutaneous adipose tissue biopsies after exercise training. In mice, exercise training increases TGF-β2 in scWAT, serum, and its secretion from fat explants. Transplanting scWAT from exercise-trained wild type mice, but not from adipose tissue-specific Tgfb2-/- mice, into sedentary mice improves glucose tolerance. TGF-β2 treatment reverses the detrimental metabolic effects of high fat feeding in mice. Lactate, a metabolite released from muscle during exercise, stimulates TGF-β2 expression in human adipocytes. Administration of the lactate-lowering agent dichloroacetate during exercise training in mice decreases circulating TGF-β2 levels and reduces exercise-stimulated improvements in glucose tolerance. Thus, exercise training improves systemic metabolism through inter-organ communication with fat via a lactate-TGF-β2-signaling cycle.

Publication types

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

MeSH terms

  • Adipokines / metabolism*
  • Adipose Tissue / metabolism
  • Animals
  • Fatty Acids / metabolism*
  • Glucose / metabolism*
  • Mice
  • Physical Conditioning, Animal*
  • Transforming Growth Factor beta2 / metabolism*

Substances

  • Adipokines
  • Fatty Acids
  • Transforming Growth Factor beta2
  • Glucose