TY - JOUR
T1 - TGF-β2 is an exercise-induced adipokine that regulates glucose and fatty acid metabolism
AU - Takahashi, Hirokazu
AU - Alves, Christiano R.R.
AU - Stanford, Kristin I.
AU - Middelbeek, Roeland J.W.
AU - Nigro, Pasquale
AU - Ryan, Rebecca E.
AU - Xue, Ruidan
AU - Sakaguchi, Masaji
AU - Lynes, Matthew D.
AU - So, Kawai
AU - Mul, Joram D.
AU - Lee, Min Young
AU - Balan, Estelle
AU - Pan, Hui
AU - Dreyfuss, Jonathan M.
AU - Hirshman, Michael F.
AU - Azhar, Mohamad
AU - Hannukainen, Jarna C.
AU - Nuutila, Pirjo
AU - Kalliokoski, Kari K.
AU - Nielsen, Søren
AU - Pedersen, Bente K.
AU - Kahn, C. Ronald
AU - Tseng, Yu Hua
AU - Goodyear, Laurie J.
PY - 2019
Y1 - 2019
N2 - 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 subcutaneous white adipose tissue (scWAT) and 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.
AB - 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 subcutaneous white adipose tissue (scWAT) and 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.
U2 - 10.1038/s42255-018-0030-7
DO - 10.1038/s42255-018-0030-7
M3 - Journal article
C2 - 31032475
AN - SCOPUS:85062910880
VL - 1
SP - 291
EP - 303
JO - Nature Metabolism
JF - Nature Metabolism
SN - 2522-5812
IS - 2
ER -