Author
Listed:
- Dongdong Wang
(McMaster University
McMaster University)
- Logan K. Townsend
(McMaster University
McMaster University)
- Geneviève J. DesOrmeaux
(University of Guelph)
- Sara M. Frangos
(University of Guelph)
- Battsetseg Batchuluun
(McMaster University
McMaster University)
- Lauralyne Dumont
(Université de Sherbrooke)
- Rune Ehrenreich Kuhre
(Novo Nordisk
University of Copenhagen)
- Elham Ahmadi
(McMaster University
McMaster University)
- Sumei Hu
(Beijing Technology and Business University
Chinese Academy of Sciences)
- Irena A. Rebalka
(McMaster University)
- Jaya Gautam
(McMaster University
McMaster University)
- Maria Joy Therese Jabile
(McMaster University
McMaster University)
- Chantal A. Pileggi
(University of Ottawa
University of Ottawa)
- Sonia Rehal
(McMaster University
McMaster University)
- Eric M. Desjardins
(McMaster University
McMaster University)
- Evangelia E. Tsakiridis
(McMaster University
McMaster University)
- James S. V. Lally
(McMaster University
McMaster University)
- Emma Sara Juracic
(University of Waterloo)
- A. Russell Tupling
(University of Waterloo)
- Hertzel C. Gerstein
(McMaster University
McMaster University
Hamilton Health Sciences and McMaster University)
- Guillaume Paré
(McMaster University
Hamilton Health Sciences and McMaster University
McMaster University, Hamilton Health Sciences
McMaster University)
- Theodoros Tsakiridis
(McMaster University
McMaster University)
- Mary-Ellen Harper
(University of Ottawa
University of Ottawa)
- Thomas J. Hawke
(McMaster University)
- John R. Speakman
(Chinese Academy of Sciences
Chinese Academy of Sciences
University of Aberdeen
CAS Center for Excellence in Animal Evolution and Genetics (CCEAEG))
- Denis P. Blondin
(Université de Sherbrooke
Université de Sherbrooke)
- Graham P. Holloway
(University of Guelph)
- Sebastian Beck Jørgensen
(Novo Nordisk
Novo Nordisk)
- Gregory R. Steinberg
(McMaster University
McMaster University
McMaster University)
Abstract
Caloric restriction that promotes weight loss is an effective strategy for treating non-alcoholic fatty liver disease and improving insulin sensitivity in people with type 2 diabetes1. Despite its effectiveness, in most individuals, weight loss is usually not maintained partly due to physiological adaptations that suppress energy expenditure, a process known as adaptive thermogenesis, the mechanistic underpinnings of which are unclear2,3. Treatment of rodents fed a high-fat diet with recombinant growth differentiating factor 15 (GDF15) reduces obesity and improves glycaemic control through glial-cell-derived neurotrophic factor family receptor α-like (GFRAL)-dependent suppression of food intake4–7. Here we find that, in addition to suppressing appetite, GDF15 counteracts compensatory reductions in energy expenditure, eliciting greater weight loss and reductions in non-alcoholic fatty liver disease (NAFLD) compared to caloric restriction alone. This effect of GDF15 to maintain energy expenditure during calorie restriction requires a GFRAL–β-adrenergic-dependent signalling axis that increases fatty acid oxidation and calcium futile cycling in the skeletal muscle of mice. These data indicate that therapeutic targeting of the GDF15–GFRAL pathway may be useful for maintaining energy expenditure in skeletal muscle during caloric restriction.
Suggested Citation
Dongdong Wang & Logan K. Townsend & Geneviève J. DesOrmeaux & Sara M. Frangos & Battsetseg Batchuluun & Lauralyne Dumont & Rune Ehrenreich Kuhre & Elham Ahmadi & Sumei Hu & Irena A. Rebalka & Jaya Gau, 2023.
"GDF15 promotes weight loss by enhancing energy expenditure in muscle,"
Nature, Nature, vol. 619(7968), pages 143-150, July.
Handle:
RePEc:nat:nature:v:619:y:2023:i:7968:d:10.1038_s41586-023-06249-4
DOI: 10.1038/s41586-023-06249-4
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Cited by:
- Xuanming Guo & Pallavi Asthana & Lixiang Zhai & Ka Wing Cheng & Susma Gurung & Jiangang Huang & Jiayan Wu & Yijing Zhang & Arun Kumar Mahato & Mart Saarma & Mart Ustav & Hiu Yee Kwan & Aiping Lyu & Ku, 2024.
"Artesunate treats obesity in male mice and non-human primates through GDF15/GFRAL signalling axis,"
Nature Communications, Nature, vol. 15(1), pages 1-14, December.
- Pavlina Chrysafi & Laura Valenzuela-Vallejo & Konstantinos Stefanakis & Theodoros Kelesidis & Margery A. Connelly & Christos S. Mantzoros, 2024.
"Total and H-specific GDF-15 levels increase in caloric deprivation independently of leptin in humans,"
Nature Communications, Nature, vol. 15(1), pages 1-15, December.
- Laurent L’homme & Benan Pelin Sermikli & Joel T. Haas & Sébastien Fleury & Sandrine Quemener & Valentine Guinot & Emelie Barreby & Nathalie Esser & Robert Caiazzo & Hélène Verkindt & Benjamin Legendre, 2024.
"Adipose tissue macrophage infiltration and hepatocyte stress increase GDF-15 throughout development of obesity to MASH,"
Nature Communications, Nature, vol. 15(1), pages 1-18, December.
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