ArticleThe Journal of biological chemistry2011
Genetic dissection of the functions of the melanocortin-3 receptor, a seven-transmembrane G-protein-coupled receptor, suggests roles for central and peripheral receptors in energy homeostasis.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 61 citations in OpenAlex.
- Melanocortin 3 receptor regulates hepatic autophagy and systemic adiposity.Nature communications · 2025Article
- Article
- 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
- Neuroanatomical dissection of the MC3R circuitry regulating energy rheostasis.bioRxiv : the preprint server for biology · 2024Article
- Organization of neural systems expressing melanocortin-3 receptors in the mouse brain: Evidence for sexual dimorphism.The Journal of comparative neurology · 2022Article
- The ventromedial hypothalamic nucleus: watchdog of whole-body glucose homeostasis.Cell & bioscience · 2022Review
- Melanocortin 3 receptor-expressing neurons in the ventromedial hypothalamus promote glucose disposal.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Immunoglobulin G modulation of the melanocortin 4 receptor signaling in obesity and eating disorders.Translational psychiatry · 2019Article
- Lateral Hypothalamic Mc3R-Expressing Neurons Modulate Locomotor Activity, Energy Expenditure, and Adiposity in Male Mice.Endocrinology · 2019Article
- Melanocortin-3 Receptors Expressed on Agouti-Related Peptide Neurons Inhibit Feeding Behavior in Female Mice.Obesity (Silver Spring, Md.) · 2018Article
- The genomic basis of environmental adaptation in house mice.PLoS genetics · 2018Article
- Pharmacological effect of human melanocortin-2 receptor accessory protein 2 variants on hypothalamic melanocortin receptors.Endocrine · 2018Article
- Bombesin-like receptor 3 (Brs3) expression in glutamatergic, but not GABAergic, neurons is required for regulation of energy metabolism.Molecular metabolism · 2017Article
- Polymorphisms and mutations in the melanocortin-3 receptor and their relation to human obesity.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- Melanocortin-3 receptors expressed in Nkx2.1(+ve) neurons are sufficient for controlling appetitive responses to hypocaloric conditioning.Scientific reports · 2017Article
- A Life without Hunger: The Ups (and Downs) to Modulating Melanocortin-3 Receptor Signaling.Frontiers in neuroscience · 2017Review
- Effects of Melanocortin 3 and 4 Receptor Deficiency on Energy Homeostasis in Rats.Scientific reports · 2016Article
- Melanocortin-3 receptors in the limbic system mediate feeding-related motivational responses during weight loss.Molecular metabolism · 2016Article
- 60 YEARS OF POMC: Regulation of feeding and energy homeostasis by α-MSH.Journal of molecular endocrinology · 2016Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
Abstract
The melanocortin-3 receptor (MC3R) gene is pleiotropic, influencing body composition, natriuresis, immune function, and entrainment of circadian rhythms to nutrient intake. MC3Rs are expressed in hypothalamic and limbic regions of the brain and in peripheral tissues. To investigate the roles of central MC3Rs, we inserted a "lox-stop-lox" (LoxTB) 5' of the translation initiation codon of the mouse Mc3r gene and reactivated transcription using neuron-specific Cre transgenic mice. As predicted based on earlier observations of Mc3r knock-out mice, Mc3r(TB/TB) mice displayed reduced lean mass, increased fat mass, and accelerated diet-induced obesity. Surprisingly, rescuing Mc3r expression in the nervous system using the Nestin-Cre transgene only partially rescued obesity in chow-fed conditions and had no impact on the accelerated diet-induced obesity phenotype. The ventromedial hypothalamus (VMH), a critical node in the neural networks regulating feeding-related behaviors and metabolic homeostasis, exhibits dense Mc3r expression relative to other brain regions. To target VMH MC3R expression, we used the steroidogenic factor-1 Cre transgenic mouse. Although restoring VMH MC3R signaling also had a modest impact on obesity, marked improvements in metabolic homeostasis were observed. VMH MC3R signaling was not sufficient to rescue the lean mass phenotype or the regulation of behaviors anticipating food anticipation. These results suggest that actions of MC3Rs impacting on energy homeostasis involve both central and peripheral sites of action. The impact of central MC3Rs on behavior and metabolism involves divergent pathways; VMH MC3R signaling improves metabolic homeostasis but does not significantly impact on the expression of behaviors anticipating nutrient availability.
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Registered trials
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