ArticleThe Journal of clinical investigation2016
G(q/11)α and G(s)α mediate distinct physiological responses to central melanocortins.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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
63 citing papers in PubMed.
- MC4R agonism promotes durable weight loss in patients with leptin receptor deficiency.Nature medicine · 2018Trial
- Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency.Molecular metabolism · 2017Trial
- 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
- Neural Melanocortin Receptors in Fish: Insights into Growth Regulation and Aquaculture Advancement.Biomolecules · 2026Review
- The role of accessory proteins and co-factors in regulation of melanocortin-4 receptor signalling: An update.Journal of neuroendocrinology · 2026Review
- A melanocortin 4- and glucagon-like peptide 1 receptor multiple agonist for the treatment of diabetes and obesity.Metabolism: clinical and experimental · 2026Article
- The melanocortin receptors as targets for general obesity: contextualizing clinical failures and analyzing future perspectives.Frontiers in endocrinology · 2026Review
- MRAP2 modifies the signaling and oligomerization state of the melanocortin-4 receptor.Nature communications · 2025Article
- Uncovering the role of Gpr45 in obesity regulation.Molecular metabolism · 2025Article
- Article
- Obesity-associated MRAP2 variants impair multiple MC4R-mediated signaling pathways.Human molecular genetics · 2025Article
- Carbocyclic setmelanotide analogs maintain biochemical potency at melanocortin 4 receptors.Journal of peptide science : an official publication of the European Peptide Society · 2025Article
- Article
- Structural basis for the ligand recognition and G protein subtype selectivity of kisspeptin receptor.Science advances · 2024Article
- A Novel Maternally InheritedJCEM case reports · 2024Article
- A Critical Functional Missense Mutation (T117M) in SheepAnimals : an open access journal from MDPI · 2024Article
- Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Activation of brain melanocortin 4 receptors (MC4Rs) leads to reduced food intake, increased energy expenditure, increased insulin sensitivity, and reduced linear growth. MC4R effects on energy expenditure and glucose metabolism are primarily mediated by the G protein G(s)α in brain regions outside of the paraventricular nucleus of the hypothalamus (PVN). However, the G protein(s) that is involved in MC4R-mediated suppression of food intake and linear growth, which are believed to be regulated primarily though action in the PVN, is unknown. Here, we show that PVN-specific loss of G(q)α and G11α, which stimulate PLC, leads to severe hyperphagic obesity, increased linear growth, and inactivation of the hypothalamic-pituitary-adrenal axis, without affecting energy expenditure or glucose metabolism. Moreover, we demonstrate that the ability of an MC4R agonist delivered to PVN to inhibit food intake is lost in mice lacking G(q/11)α in the PVN but not in animals deficient for G(s)α. The blood pressure response to the same MC4R agonist was only lost in animals lacking G(s)α specifically in the PVN. Together, our results exemplify how different physiological effects of GPCRs may be mediated by different G proteins and identify a pathway for appetite regulation that could be selectively targeted by G(q/11)α-biased MC4R agonists as a potential treatment for obesity.
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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 OpenQuestion graph.