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Region Hovedstaden - en del af Københavns Universitetshospital
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TGF-β2 is an exercise-induced adipokine that regulates glucose and fatty acid metabolism

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  • Hirokazu Takahashi
  • Christiano R R Alves
  • Kristin I Stanford
  • Roeland J W Middelbeek
  • Pasquale Nigro
  • Rebecca E Ryan
  • Ruidan Xue
  • Masaji Sakaguchi
  • Matthew D Lynes
  • Kawai So
  • Joram D Mul
  • Min-Young Lee
  • Estelle Balan
  • Hui Pan
  • Jonathan M Dreyfuss
  • Michael F Hirshman
  • Mohamad Azhar
  • Jarna C Hannukainen
  • Pirjo Nuutila
  • Kari K Kalliokoski
  • Søren Nielsen
  • Bente K Pedersen
  • C Ronald Kahn
  • Yu-Hua Tseng
  • Laurie J Goodyear
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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.

OriginalsprogEngelsk
TidsskriftJournal of Nutrition and Metabolism
Vol/bind1
Udgave nummer2
Sider (fra-til)291-303
Antal sider13
ISSN1743-7075
DOI
StatusUdgivet - feb. 2019

ID: 59100897