Obesity due to MC4R deficiency is associated with reduced cholesterol, triglycerides and cardiovascular disease risk.

ABSTRACT: Obesity causes dyslipidemia and is a major risk factor for cardiovascular disease. However, the mechanisms coupling weight gain and lipid metabolism are poorly understood. Brain melanocortin 4 receptors (MC4Rs) regulate body weight and lipid metabolism in mice, but the relevance of these findings to humans is unclear. Here we investigated lipid levels in men and women with obesity due to MC4R deficiency. Among 7,719 people from the Genetics of Obesity Study cohort, we identified 316 probands and 144 adult family members with loss-of-function (LoF) MC4R mutations. Adults with MC4R deficiency had lower levels of total and low-density lipoprotein (LDL)-cholesterol and triglycerides than 336,728 controls from the UK Biobank, after adjusting for adiposity. Carriers of LoF MC4R variants within t

SUBMITTER: Zorn S 

PROVIDER: S-EPMC12705457 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature