ArticleNature medicine2025
Obesity due to MC4R deficiency is associated with reduced cholesterol, triglycerides and cardiovascular disease risk.
Article in Nature medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed.
- Tirzepatide leads to weight reduction in people with obesity due to MC4R deficiency.Nature medicine · 2025Trial
- Genetics of MASLD: a diabetes perspective.Diabetologia · 2026Review
- Shared and distinct genetic architectures of eating disorders and obesity: From monogenic causes to polygenic risk.Reviews in endocrine & metabolic disorders · 2026Review
- Recent developments in GPCR signalling in appetite regulation.Bioscience reports · 2026Review
- Primary cilia and neural computation.Journal of biomedical science · 2026Review
- Management of Childhood Obesity.International journal of molecular sciences · 2026Review
- Article
- Molecularly defined subpopulations of leptin receptor neurons dissociate the control of food intake from blood pressure.bioRxiv : the preprint server for biology · 2026Article
- Exploring Autosomal Dominant Non-Syndromic Monogenic Obesity: From Genes to Therapy.Current issues in molecular biology · 2026Review
- Monogenic obesity due to MC4R deficiency: lessons from a multigenerational case.Molecular and cellular pediatrics · 2026Article
Corrections and comments
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Authors and funding
16 authors.
Funding
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 the UK Biobank had lower lipid levels and a lower risk of cardiovascular disease, after accounting for body weight, compared to noncarriers. After a high-fat meal, the postprandial rise in triglyceride-rich lipoproteins and metabolomic markers of fatty acid oxidation were reduced in people with MC4R deficiency compared to controls, changes that favor triglyceride storage in adipose tissue. We concluded that central MC4Rs regulate lipid metabolism and cardiovascular disease risk in humans, highlighting potential therapeutic approaches for cardiovascular risk reduction.
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