Hormonal
Elevated plasma levels of GDF15 and its receptors (RET and GFRAL) mediate the causal relationship between smoking intensity and reduced adiposity (lower BMI and body fat percentage).
Smoking suppresses weight partly through the GDF15 protein pathway. When people quit, this pathway downregulates, potentially leading to weight gain. Future treatments might target GDF15 (e.g., using drugs like metformin to boost it) to help people quit without gaining weight, rather than relying solely on nicotine replacement.
SomaScan_GDF15 partially mediated the associations of smoking with all adiposity measures, while Olink_GDF15 mediated the association with body fat percentage. The GDF15/RET ratio more robustly mediated the smoking-adiposity relationships than GDF15 alone in both platforms.
Why this rating
The study uses a large prospective cohort (China Kadoorie Biobank), two proteomic platforms, and Mendelian Randomization to establish causality, though it is observational in nature regarding the protein levels.
Source
GDF15 and its receptors as pathways mediating smoking related weight change
Alexander Clive Tinworth et al. · EBioMedicine · 2025
DOI 10.1016/j.ebiom.2025.105806
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