Weight Loss Secret Weapon: GDF15 fuels calories burned while dieting

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McMaster University researchers found that the GDF15 hormone, previously linked to reduced appetite from metformin, could also help with weight loss by maintaining metabolism while dieting. This could lead to better weight-loss therapies and offer insights into individual variations in diet success.

The research opens up new possibilities to help people maintain weight loss after dieting.

Researchers led by McMaster University professor Gregory Steinberg and postdoctoral researcher Dongdong Wang have uncovered a key mechanism to promote weight loss and maintain calorie burning during dieting.

The research team studied a hormone called GDF15 that had previously been shown to reduce appetite in response to the type 2 diabetes drug metformin. Their latest findings, published in Nature on June 28, it demonstrated that GDF15 also has the potential to help with weight loss.

The research opens up new possibilities to help people maintain weight loss after dieting, as well as the potential to develop combination therapies with GDF15 and currently available drugs that suppress appetite to promote further weight loss. Obesity, a global concern affecting one billion people, is linked to many metabolic disorders, including type 2 diabetes. It has long been the subject of research into effective weight loss methods.

Dongdong Wang, first author and postdoctoral researcher; and Gregory Steinberg, professor of medicine at McMaster University and co-director of the Center for Metabolism, Obesity, and Diabetes Research at McMaster University. Credit: McMaster University

We found that in mice, GDF15 blocks the metabolic slowdown that occurs during dieting by increasing the futile cycling of calcium in muscle, said Steinberg, a professor in the McMaster University Department of Medicine and co-director of the Center for Metabolism, Obesity, and Research. about diabetes.

Our study highlights the potential of the GDF15 hormone to not only reduce the desire to eat fatty foods, but also to simultaneously increase energy expenditure in the muscles.

While calorie restriction initially leads to weight loss, the body’s metabolism eventually slows down this process, reducing its effectiveness. The research showed, however, that the GDF15-treated mice continued to lose weight while consuming the same number of calories as the control group. This increase in energy expenditure occurred in their muscles but not in their fat tissue.

More research is needed to confirm these findings in humans, Steinberg said. He said understanding how GDF15 levels affect muscle energy expenditure in humans could help explain why people have varying levels of success at losing weight with diet.

Additional research into GDF15 could also provide new ways to help people struggling to lose weight through traditional diets, and could extend the benefits of recently approved appetite-suppressing drugs that target the GLP1 receptor.

Reference: GDF15 Promotes Weight Loss by Improving Energy Expenditure in Muscles By Dongdong Wang, Logan K. Townsend, Genevive J. DesOrmeaux, Sara M. Frangos, Battsetseg Batchuluun, Lauralyne Dumont, Rune Ehrenreich Kuhre, Elham Ahmadi, Sumei Hu, Irena A. Rebalka, Jaya Gautam, Maria Joy Therese Jabile, Chantal A. Pileggi, Sonia Rehal, Eric M. Desjardins, Evangelia E. Tsakiridis, James SV Lally, Emma Sara Juracic, A. Russell Tupling, Hertzel C. Gerstein, Guillaume Par , Theodoros Tsakiridis, Mary-Ellen Harper, Thomas J. Hawke, John R. Speakman, Denis P. Blondin, Graham P. Holloway, Sebastian Beck Jrgensen, and Gregory R. Steinberg, June 28, 2023, Nature.
DOI: 10.1038/s41586-023-06249-4

This analysis of the impact of GDF15 on weight loss is the result of a collaboration with Novo Nordisk and researchers in Ottawa, Waterloo, Sherbrooke, Beijing and Guelph.

This work was funded in part by Diabetes Canada, Canadian Institutes of Health Research and Novo Nordisk.