The 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 diabetes. 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 unclear.
Researchers at McMaster University have uncovered a key mechanism for promoting weight loss and maintaining the burning of calories during dieting. The study team looked at a hormone called GDF15 that they had previously found to suppress hunger in response to the metformin treatment for type 2 diabetes. Their most recent research, released in Nature on June 28, indicated that GDF15 may also aid in weight loss.
The study could open new avenues for developing combination therapies with GDF15 and currently available drugs that suppress appetite and promote further weight loss.
McMaster University professor Gregory Steinberg said, “We have discovered that in mice, GDF15 blocks the slowing of metabolism that occurs during dieting by ramping up calcium futile cycling in muscle. Our study highlights the potential of the hormone GDF15 to reduce the desire to eat fatty foods and simultaneously boost energy burning in muscle.”
Calorie restriction causes weight reduction at first, but with time, the body’s metabolism slows this process and makes it less effective. However, the study found that mice given GDF15 continued to lose weight even when they consumed the same number of calories as the control group. Their muscles experienced this increase in energy expenditure, but not their adipose tissue.
Further research could confirm these findings. Understanding how GDF15 levels affect muscle energy burning in people may shed light on why different dieters have varying degrees of success in losing weight.
Additional studies on GDF15 may also aid people who have trouble losing weight through conventional diets and may increase the effects of recently approved GLP1 receptor-targeted appetite suppressants.
Journal Reference:
- Wang, D., Townsend, L.K., DesOrmeaux, G.J., et al. GDF15 promotes weight loss by enhancing energy expenditure in muscle. Nature (2023). DOI: 10.1038/s41586-023-06249-4