ArticleScience advances2018
Regulation of energy rheostasis by the melanocortin-3 receptor.
Article in Science advances, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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
40 citing papers in PubMed, 59 citations in OpenAlex.
- Genetic variants of the leptin-melanocortin pathway in a clinically selected Greek cohort with severe early-onset obesity and hyperphagia: implications for precision obesity medicine.Obesity pillars · 2026Article
- Recent developments in GPCR signalling in appetite regulation.Bioscience reports · 2026Review
- Neural Melanocortin Receptors in Fish: Insights into Growth Regulation and Aquaculture Advancement.Biomolecules · 2026Review
- Beyond satiety: unraveling the complex roles of POMC neurons in behavior and metabolism.Reviews in endocrine & metabolic disorders · 2026Review
- Sex-differential associations of MC3R p.F45S with human metabolic profile.Journal of neuroendocrinology · 2026Article
- Dual activation of MC3R and MC4R drives weight loss and reduces food intake in male primates with obesity.Nature communications · 2026Article
- Effect of a partial loss of function MC3R mutation on MC3R+GHSR-1A heterodimer activity and RNF11 regulation.Journal of endocrinological investigation · 2026Article
- The accessory protein MRAP2 directly interacts with melanocortin-3 receptor to enhance signaling.Science signaling · 2025Article
- Melanocortin 3 receptor regulates hepatic autophagy and systemic adiposity.Nature communications · 2025Article
- Medial hypothalamic MC3R signalling regulates energy rheostasis in adult mice.The Journal of physiology · 2025Article
- GPCRs in hypothalamic neurons and their roles in controlling food intake and metabolism.Frontiers in molecular neuroscience · 2025Review
- Fasting-induced activity changes in MC3R neurons of the paraventricular nucleus of the thalamus.Life science alliance · 2024Article
- Alx3 deficiency disrupts energy homeostasis, alters body composition, and impairs hypothalamic regulation of food intake.Cellular and molecular life sciences : CMLS · 2024Article
- Subthreshold activation of the melanocortin system causes generalized sensitization to anorectic agents in mice.The Journal of clinical investigation · 2024Article
- Neuroanatomical dissection of the MC3R circuitry regulating energy rheostasis.bioRxiv : the preprint server for biology · 2024Article
- Protection against overfeeding-induced weight gain is preserved in obesity but does not require FGF21 or MC4R.Nature communications · 2024Article
- Melanocortin-3 receptor expression in AgRP neurons is required for normal activation of the neurons in response to energy deficiency.Cell reports · 2023Article
- Paraventricular ThalamicThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Targeting the central melanocortin system for the treatment of metabolic disorders.Nature reviews. Endocrinology · 2023Review
- Structural insights into ligand recognition and subtype selectivity of the human melanocortin-3 and melanocortin-5 receptors.Cell discovery · 2023Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 3 countries.
Funding
Abstract
Like most homeostatic systems, adiposity in mammals is defended between upper and lower boundary conditions. While leptin and melanocortin-4 receptor (MC4R) signaling are required for defending energy set point, mechanisms controlling upper and lower homeostatic boundaries are less well understood. In contrast to the MC4R, deletion of the MC3R does not produce measurable hyperphagia or hypometabolism under normal conditions. However, we demonstrate that MC3R is required bidirectionally for controlling responses to external homeostatic challenges, such as caloric restriction or calorie-rich diet. MC3R is also required for regulated excursion from set point, or rheostasis, during pregnancy. Further, we demonstrate a molecular mechanism: MC3R provides regulatory inputs to melanocortin signaling, acting presynaptically on agouti-related protein neurons to regulate γ-aminobutyric acid release onto anorexigenic MC4R neurons, exerting boundary control on the activity of MC4R neurons. Thus, the MC3R is a critical regulator of boundary controls on melanocortin signaling, providing rheostatic control on energy storage.
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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.