| First Author | Wang D | Year | 2023 |
| Journal | Nature | Volume | 619 |
| Issue | 7968 | Pages | 143-150 |
| PubMed ID | 37380764 | Mgi Jnum | J:340165 |
| Mgi Id | MGI:7525782 | Doi | 10.1038/s41586-023-06249-4 |
| Citation | Wang D, et al. (2023) GDF15 promotes weight loss by enhancing energy expenditure in muscle. Nature 619(7968):143-150 |
| abstractText | 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(1). 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(2,3). 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 alpha-like (GFRAL)-dependent suppression of food intake(4-7). 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-beta-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. |
