A1 Refereed original research article in a scientific journal
TGF-β2 is an exercise-induced adipokine that regulates glucose and fatty acid metabolism
Authors: Takahashi H, Alves CRR, Stanford KI, Middelbeek RJW, Nigro P, Ryan RE, Xue RD, Sakaguchi M, Lynes MD, So KW, Mul JD, Lee MY, Balan E, Pan H, Dreyfuss JM, Hirshman MF, Azhar M, Hannukainen JC, Nuutila P, Kalliokoski KK, Nielsen S, Pedersen BK, Kahn CR, Tseng YH, Goodyear LJ, Goodyear LJ
Publisher: NATURE PUBLISHING GROUP
Publication year: 2019
Journal: Nature Metabolism
Journal name in source: NATURE METABOLISM
Journal acronym: NAT METAB
Volume: 1
Issue: 2
First page : 291
Last page: 303
Number of pages: 13
DOI: https://doi.org/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-beta 2 (TGF-beta 2) is secreted from adipose tissue in response to exercise and improves glucose tolerance in mice. We identify TGF-beta 2 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-beta 2 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-beta 2 treatment reverses the detrimental metabolic effects of high-fat feeding in mice. Lactate, a metabolite released from muscle during exercise, stimulates TGF-beta 2 expression in human adipocytes. Administration of the lactate-lowering agent dichloroacetate during exercise training in mice decreases circulating TGF-beta 2 levels and reduces exercise-stimulated improvements in glucose tolerance. Thus, exercise training improves systemic metabolism through interorgan communication with fat via a lactate-TGF-beta 2 signaling cycle.
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-beta 2 (TGF-beta 2) is secreted from adipose tissue in response to exercise and improves glucose tolerance in mice. We identify TGF-beta 2 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-beta 2 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-beta 2 treatment reverses the detrimental metabolic effects of high-fat feeding in mice. Lactate, a metabolite released from muscle during exercise, stimulates TGF-beta 2 expression in human adipocytes. Administration of the lactate-lowering agent dichloroacetate during exercise training in mice decreases circulating TGF-beta 2 levels and reduces exercise-stimulated improvements in glucose tolerance. Thus, exercise training improves systemic metabolism through interorgan communication with fat via a lactate-TGF-beta 2 signaling cycle.
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