Researchers at McMaster University have uncovered a key mechanism for promoting weight loss and maintaining the burning of calories during dieting, according to a paper published recently in Nature.
Researchers led by Gregory R. Steinberg, PhD, a professor of the Department of Medicine at McMaster University and co-director of the Centre for Metabolism, Obesity, and Diabetes Research, and Dongdong Wang, PhD, a postdoctoral research fellow, studied growth differentiating factor 15 (GDF15). GDF15 has been shown to lower adiposity by primarily suppressing food intake in rodents and non-human primates, but the authors write that other distinctions must be considered before concluding this is the sole reason for weight loss.
The researchers point out that the most important of these distinctions is that “energy intake, energy expenditure and body weight are interdependent variables that are dynamically linked to each other, in that, reductions in energy intake and weight loss can both lead to reduced energy expenditure.” Specifically, previous studies in mice treated with recombinant GDF15 and calorically matched controls were conducted over a relatively short period (7-14 days) before potential reductions in energy expenditure, a process known as adaptive thermogenesis, may have occurred. In addition, previous studies had beencompleted in mice housed at room temperature (21 degrees Celsius — below the thermoneutral zone for rodents)which may have also masked potential changes in adaptive thermogenesis. “Collectively, these studies indicate that it is important to consider the interrelationships between caloric intake, duration of intervention and housing temperature when studying weight loss and pharmacological interventions in mice,” the authors write.
For this study, the researchers analyzed mice housed at thermoneutrality (29 degrees Celsius) that were fed a western-style diet that promotes obesity, insulin resistance, and non-alcoholic steatohepatitis (NASH). The mice were then injected with recombinant human GDF15 at the start of the light cycle (the time period when mice eat fewer calories, as opposed to previous studies where mice were injected at the start of the dark cycle.
The researchers found that like previous studies, over the first two weeks GDF15 suppressed food intake and weight loss was comparable to mice that were fed the same amount of food and injected with a vehicle control. However, after two weeks, the mice treated with GDF15 continued losing weight while those consuming the same number of calories stopped losing weight, indicating that GDF15 was blocking the reductions in energy expenditure (adaptive thermogenesis) that occurs during caloric restriction. This maintenance of energy expenditure in GDF15 treated mice, occurred in their muscles but not fat tissue and was related to increases in calcium futile cycling.
More research is needed to confirm these findings in humans, Steinberg says. He says 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 exercise or recently approved appetite suppressing drugs that target the GLP1 receptor.
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