The DOI matches its Crossref record; 64 of the 66 references it cites were found in a registry or an index.
TGF-β2 is an exercise-induced adipokine that regulates glucose and fatty acid metabolism
Open accessAbstract
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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“Transforming growth factor-beta 2 (TGF-β2), an exercise-induced adipokine, is stimulated by exercise-induced lactate, enhancing glucose uptake in skeletal muscle and boosting mitochondrial function, shedding light on adipose–muscle tissue crosstalk [79] (Table 1).”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [79]
In the citing paper
“Moreover, exercise-trained WAT fosters the generation of thermogenic brown-like adipocytes with specific adipokines, including TGF-β [79], apelin, follistatin, and myostatin (Figure 3) [80,81].”
From Exerkines and Sarcopenia: Unveiling the Mechanism Behind Exercise-Induced Mitochondrial Homeostasis (2025) · cites this paper as [79]
In the citing paper
“Exercise-related paracrine effects are also observed in the nervous system53, adipose tissue42,54–58, bone59–61, cartilage62, extracellular matrix63,64 and the immune system65,66.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [42]
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“In a mouse model, specific lactate exposure in vitro and in vivo increased adipocyte expression of TGFβ2 (REF.42).”
From Exerkines in health, resilience and disease (2022) · cites this paper as [42]
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“in a mouse model of chronic exercise, increased adipocyte levels of TGFβ2 expression and secretion were associated with improvements in glucose metabolism, lipid oxidation and a possible reduction of adipose tissue inflammation.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [42]
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“Parallel findings were also observed in humans undertaking chronic exercise, albeit to a less pronounced degree than the animal model observations42.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [42]
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Skeletal muscle energy metabolism during exercise
Hargreaves, M., & Spriet, L. L. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0251-4 · Cited by 1,408
Exerkines in health, resilience and disease
Chow, L. S., Gerszten, R. E., Taylor, J. M., Pedersen, B. K., van Praag, H., Trappe, S., Febbraio, M. A., Galis, Z. S., Gao, Y., Haus, J. M., et al. (2022) · Nature Reviews Endocrinology · doi:10.1038/s41574-022-00641-2 · Cited by 927
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BackgroundLactate as a fulcrum of metabolism
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Metadata
- Authors
- Takahashi, H., Alves, C. R. R., Stanford, K. I., Middelbeek, R. J. W., Nigro, P., Ryan, R. E., Xue, R., Sakaguchi, M., Lynes, M. D., So, K., Mul, J. D., Lee, M.-Y., Balan, E., Pan, H., Dreyfuss, J. M., Hirshman, M. F., Azhar, M., Hannukainen, J. C., Nuutila, P., Kalliokoski, K. K., Nielsen, S., Pedersen, B. K., Kahn, C. R., Tseng, Y.-H., & Goodyear, L. J.
- Affiliations
- Joslin Diabetes Center (US)
- University of South Carolina (US)
- University of Turku (FI)
- University of Copenhagen (DK)
- Corresponding author
- Goodyear, Laurie J.
- ORCID
- Takahashi, Hirokazu
- Alves, Christiano R. R.
- Stanford, Kristin I.
- Middelbeek, Roeland J. W.
- Nigro, Pasquale
- Sakaguchi, Masaji
- Lynes, Matthew D.
- Mul, Joram D.
- Pan, Hui
- Dreyfuss, Jonathan M.
- Hirshman, Michael F.
- Azhar, Mohamad
- Hannukainen, Jarna C.
- Nuutila, Pirjo
- Kalliokoski, Kari K.
- Nielsen, Søren
- Pedersen, Bente K.
- Kahn, C. Ronald
- Tseng, Yu-Hua
- Goodyear, Laurie J.
- Venue
- Nature Metabolism
- Published
- 2019-02-11
- Volume
- 1
- Issue
- 2
- Pages
- 291-303
- ISSN
- 2522-5812 (ISSN-L)
- PMC
- PMC6481955
- OpenAlex
- W2912468419
- Cited by
- 204
- References
- 66
- Citations by year
- 2026: 16 · 2025: 25 · 2024: 34 · 2023: 31 · 2022: 31 · 2021: 33 · 2020: 22 · 2019: 10
- FWCI
- 18.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Metabolism (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, other-oa)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association (R01HL126705, 17GRNT33650018, R01DK102898)
- Joslin Diabetes Center (P30DK36836, K23-DK114550)
- TrygFonden
- National Institutes of Health (17GRNT33650018, DK 36836, 5r01dk112283-03)
- Japan Society for the Promotion of Science (18K16208)
- National Heart, Lung, and Blood Institute (R01HL126705, R01HL138738, R01HL145064)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK112283, R01DK077097, R01DK102898, K01DK111714, K23DK114550, R01DK033201, F32DK102320, T32DK007260, R01DK101043, P30DK036836, R01DK082659, R01DK099511)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Keywords
- TGF-beta2, glucose tolerance, fatty acid metabolism, subcutaneous white adipose tissue, lactate, dichloroacetate, inter-organ communication, myokines, high-fat feeding, exercise training, adipocytes
- MeSH terms
- Adipose Tissue, Animals, Fatty Acids, Glucose, Physical Conditioning, Animal, Mice, Transforming Growth Factor beta2, Adipokines
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