Obesity due to MC4R deficiency is associated with reduced cholesterol, triglycerides and cardiovascular disease risk
Authors' conclusion
We concluded that central MC4Rs regulate lipid metabolism and cardiovascular disease risk in humans
Study context
- Population
- People from the Genetics of Obesity Study cohort with obesity due to MC4R deficiency (316 probands, 144 adult family members); UK Biobank316 probands · 144 adult relatives
- Comparison
- Adults with loss-of-function (LoF) MC4R mutations vs controls/noncarriers
- Controlsn = 336,728reference
- Outcome
- Lipid levels
Methodological detailscase–control comparison with UK Biobank controls, adjusted for adiposity, high-fat meal challenge
- Case–control comparison with UK Biobank controls
- Adjusted for adiposity
- High-fat meal challenge
Main finding
As reported in the abstract
Total cholesterol, LDL-C and TG (adjusted for adiposity)
- Adults with MC4R deficiency had lower total and LDL-C and TG than UK Biobank controls, after adjusting for adiposity
Further findings
Lipid levels and CVD risk in UK Biobank LoF MC4R variant carriers
- Carriers had lower lipid levels and lower CVD risk vs noncarriers, after accounting for body weight
Postprandial response to high-fat meal
- Postprandial rise in TG-rich lipoproteins and metabolomic markers of fatty acid oxidation reduced in MC4R deficiency vs controls
Original publication
Obesity due to MC4R deficiency is associated with reduced cholesterol, triglycerides and cardiovascular disease risk. Nat Med. Published 16 October 2025. doi:10.
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