Research
Energy balance
GDF15 maintains energy expenditure and promotes weight loss through a GFRAL-dependent signaling axis that activates beta-adrenergic receptors in skeletal muscle, increasing fatty acid oxidation and calcium futile cycling.
The weight loss benefits of GDF15 rely on a specific biological pathway involving the GFRAL receptor and beta-adrenergic signaling in muscles. If this pathway is blocked or missing, the energy expenditure benefits are lost.
StrongSupportsHIGH confidence
This effect of GDF15 to maintain energy expenditure during calorie restriction requires a GFRAL–β-adrenergic-dependent signalling axis that increases fatty acid oxidation and calcium futile cycling in the skeletal muscle of mice.
Why this rating
Validated using GFRAL-KO and Beta-less mice, providing strong causal evidence.
Source
GDF15 promotes weight loss by enhancing energy expenditure in muscle
Dongdong Wang et al. · Nature · 2023
DOI 10.1038/s41586-023-06249-4
mechanism_onlyCited 225×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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