2. Academic Validation
  3. TGF-β2 is an exercise-induced adipokine that regulates glucose and fatty acid metabolism

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.
Hirokazu Takahashi # 1,  Christiano R R Alves # 1,  Kristin I Stanford 1 2,  Roeland J W Middelbeek 1,  Pasquale Nigro 1,  Rebecca E Ryan 1,  Ruidan Xue 1,  Masaji Sakaguchi 1,  Matthew D Lynes 1,  Kawai So 1,  Joram D Mul 1,  Min-Young Lee 1,  Estelle Balan 1,  Hui Pan 3,  Jonathan M Dreyfuss 3,  Michael F Hirshman 1,  Mohamad Azhar 4,  Jarna C Hannukainen 5,  Pirjo Nuutila 5,  Kari K Kalliokoski 5,  Søren Nielsen 6,  Bente K Pedersen 6,  C Ronald Kahn 1,  Yu-Hua Tseng 1,  Laurie J Goodyear 7
Affiliations

Affiliations

  • 1 Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
  • 2 Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
  • 3 Bioinformatics Core, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA.
  • 4 Department of Cell Biology and Anatomy, School of Medicine, University of South Carolina, Columbia, SC, USA.
  • 5 Turku PET Centre, University of Turku, Turku, Finland.
  • 6 The Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
  • 7 Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA. [email protected].
  • # Contributed equally.
PMID: 31032475 DOI: 10.1038/s42255-018-0030-7
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.

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