ArticleThe Journal of clinical investigation2024
Subthreshold activation of the melanocortin system causes generalized sensitization to anorectic agents 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 10 papers.
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Who cites it
10 citing papers in PubMed.
- The causes of cachexia: key signals and the brain.Nature reviews. Endocrinology · 2026Review
- Structural and functional studies of inward rectifier Kir7.1 and its regulation by the Melanocortin-4 receptor.Nature communications · 2026Article
- Sex-differential associations of MC3R p.F45S with human metabolic profile.Journal of neuroendocrinology · 2026Article
- Effect of a partial loss of function MC3R mutation on MC3R+GHSR-1A heterodimer activity and RNF11 regulation.Journal of endocrinological investigation · 2026Article
- Exploring Autosomal Dominant Non-Syndromic Monogenic Obesity: From Genes to Therapy.Current issues in molecular biology · 2026Review
- Mechanisms of glucagon-like-peptide 1 in the brain beyond metabolic effects.Annals of pediatric endocrinology & metabolism · 2025Article
- Pro-Opiomelanocortin and Melanocortin Receptor 3 and 4 Mutations in Genetic Obesity.Biomolecules · 2025Review
- Medial hypothalamic MC3R signalling regulates energy rheostasis in adult mice.The Journal of physiology · 2025Article
- Structure of the Ion Channel Kir7.1 and Implications for its Function in Normal and Pathophysiologic States.bioRxiv : the preprint server for biology · 2024Article
- Neuroanatomical dissection of the MC3R circuitry regulating energy rheostasis.bioRxiv : the preprint server for biology · 2024Article
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Funding
Abstract
The melanocortin-3 receptor (MC3R) regulates GABA release from agouti-related protein (AgRP) nerve terminals and thus tonically suppresses multiple circuits involved in feeding behavior and energy homeostasis. Here, we examined the role of the MC3R and the melanocortin system in regulating the response to various anorexigenic agents. The genetic deletion or pharmacological inhibition of the MC3R, or subthreshold doses of an MC4R agonist, improved the dose responsiveness to glucagon-like peptide 1 (GLP1) agonists, as assayed by inhibition of food intake and weight loss. An enhanced anorectic response to the acute satiety factors peptide YY (PYY3-36) and cholecystokinin (CCK) and the long-term adipostatic factor leptin demonstrated that increased sensitivity to anorectic agents was a generalized result of MC3R antagonism. We observed enhanced neuronal activation in multiple hypothalamic nuclei using Fos IHC following low-dose liraglutide in MC3R-KO mice (Mc3r-/-), supporting the hypothesis that the MC3R is a negative regulator of circuits that control multiple aspects of feeding behavior. The enhanced anorectic response in Mc3r-/- mice after administration of GLP1 analogs was also independent of the incretin effects and malaise induced by GLP1 receptor (GLP1R) analogs, suggesting that MC3R antagonists or MC4R agonists may have value in enhancing the dose-response range of obesity therapeutics.
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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 OpenQuestion graph.