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

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

Author information

1
Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.
2
Department of Physiology and Cell Biology, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
3
Bioinformatics Core, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts, USA.
4
Department of Cell Biology & 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, Denmark.

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.

PMID:
31032475
PMCID:
PMC6481955
[Available on 2019-08-11]
DOI:
10.1038/s42255-018-0030-7

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