Weight Loss’ Secret Weapon: GDF15 Powers Calorie Burn During Dieting

Researchers at McMaster University have found that the hormone GDF15, previously linked to reduced appetite due to metformin, could also help with weight loss by maintaining metabolism during dieting. This could lead to improved weight loss therapies and offer insights into individual variations in dieting success.

Research opens new possibilities to help people maintain weight loss after dieting.

Researchers led by McMaster University professor Gregory Steinberg and postdoctoral research fellow Dongdong Wang have uncovered a key mechanism for promoting weight loss and maintaining the burning of calories during dieting.

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

The research opens 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 a target of research on effective weight loss methods.

Dongdong Wang, first author and postdoctoral research fellow and Gregory Steinberg, professor of Medicine at McMaster University and co-director of the Centre for Metabolism, Obesity, and Diabetes Research at McMaster University. Credit: McMaster University

“We have discovered that in mice, GDF15 blocks the slowing of metabolism that occurs during dieting by ramping up calcium futile cycling in muscle,” said Steinberg, a professor of the Department of Medicine at McMaster University and co-director of the Centre for Metabolism, Obesity, and Diabetes Research.

“Our study highlights the potential of the hormone GDF15 to not only reduce the desire to eat fatty foods but also simultaneously boost energy burning in muscle.”

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

More research is needed to confirm these findings in humans, said Steinberg. He said that understanding how GDF15 levels impact muscle energy burning in humans could help explain why people have diverse levels of success in losing weight with dieting.

Further research on GDF15 might also provide new ways to help individuals who struggle to lose weight through traditional diets and may extend the benefits of recently approved appetite-suppressing drugs that target the GLP1 receptor.

Reference: “GDF15 promotes weight loss by enhancing energy expenditure in muscle” by 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 Gautam, Maria Joy Therese Jabile, Chantal A. Pileggi, Sonia Rehal, Eric M. Desjardins, Evangelia E. Tsakiridis, James S. V. Lally, Emma Sara Juracic, A. Russell Tupling, Hertzel C. Gerstein, Guillaume Paré, Theodoros Tsakiridis, Mary-Ellen Harper, Thomas J. Hawke, John R. Speakman, Denis P. Blondin, Graham P. Holloway, Sebastian Beck Jørgensen and Gregory R. Steinberg, 28 June 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 from Ottawa, Waterloo, Sherbrooke, Beijing, and Guelph.

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

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