ArticleThe Journal of clinical investigation2024
A human obesity-associated MC4R mutation with defective Gq/11α signaling leads to hyperphagia in mice.
Article in The Journal of clinical investigation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Impact of Bariatric Surgery on the Expression of Fertility-Related Genes in Obese Women: A Systematic Review ofInternational journal of molecular sciences · 2025Pooled it
- Rationale of renewed efforts in developing MC4R modulators to treat metabolic disorders.Acta pharmaceutica Sinica. B · 2026Review
- Cardiometabolic regulation by adipocyte-derived leptin and the brain melanocortin system.Clinical science (London, England : 1979) · 2026Review
- Recent developments in GPCR signalling in appetite regulation.Bioscience reports · 2026Review
- Mice lacking β-arrestin-2 in melanocortin 4 receptor-expressing neurons show marked metabolic deficits.JCI insight · 2026Article
- Massively parallel functional genomic assays in endocrinology: from promise to delivery.Journal of molecular endocrinology · 2026Review
- The role of accessory proteins and co-factors in regulation of melanocortin-4 receptor signalling: An update.Journal of neuroendocrinology · 2026Review
- Molecular remodeling of the myocardium in mice with melanocortin-4 receptor deletion before cardiac function impairment.PloS one · 2026Article
- The melanocortin receptors as targets for general obesity: contextualizing clinical failures and analyzing future perspectives.Frontiers in endocrinology · 2026Review
- Maternal monosaccharide diets modulate melanocortin-4 receptor signaling and metabolic state in rat offspring.Pharmacological reports : PR · 2025Article
- A peptide display system identifies a potent mutant β-melanocyte-stimulating hormone agonist of melanocortin-4 receptor.Cell genomics · 2025Article
- MRAP2 modifies the signaling and oligomerization state of the melanocortin-4 receptor.Nature communications · 2025Article
- Neuroendocrinology and the Genetics of Obesity.Endocrinology · 2025Review
- Navigating the Strengths and Constraints of Mouse Models in Obesity Research.Endocrinology · 2025Review
- GPR45 modulates GαScience (New York, N.Y.) · 2025Article
- Article
- Identification and molecular characterization of missense mutations in orphan G protein-coupled receptor GPR61 occurring in severe obesity.Molecular pharmacology · 2025Article
- Obesity-associated MRAP2 variants impair multiple MC4R-mediated signaling pathways.Human molecular genetics · 2025Article
- The Interplay of Genetic Predisposition, Circadian Misalignment, and Metabolic Regulation in Obesity.Current obesity reports · 2025Review
- Carbocyclic setmelanotide analogs maintain biochemical potency at melanocortin 4 receptors.Journal of peptide science : an official publication of the European Peptide Society · 2025Article
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 3 countries.
Funding
Abstract
Melanocortin 4 receptor (MC4R) mutations are the most common cause of human monogenic obesity and are associated with hyperphagia and increased linear growth. While MC4R is known to activate Gsα/cAMP signaling, a substantial proportion of obesity-associated MC4R mutations do not affect MC4R/Gsα signaling. To further explore the role of specific MC4R signaling pathways in the regulation of energy balance, we examined the signaling properties of one such mutant, MC4R (F51L), as well as the metabolic consequences of MC4RF51L mutation in mice. The MC4RF51L mutation produced a specific defect in MC4R/Gq/11α signaling and led to obesity, hyperphagia, and increased linear growth in mice. The ability of a melanocortin agonist to acutely inhibit food intake when delivered to the paraventricular nucleus (PVN) was lost in MC4RF51L mice, as well as in WT mice in which a specific Gq/11α inhibitor was delivered to the PVN; this provided evidence that a Gsα-independent signaling pathway, namely Gq/11α, significantly contributes to the actions of MC4R on food intake and linear growth. These results suggest that a biased MC4R agonist that primarily activates Gq/11α may be a potential agent to treat obesity with limited untoward cardiovascular and other side effects.
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What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.