ArticlePloS one2012
Regulation of lean mass, bone mass, and exercise tolerance by the central melanocortin system.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 2 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 2 syntheses or guidelines pooled it, 21 citations in OpenAlex.
- Identification of pleiotropic loci underlying hip bone mineral density and trunk lean mass.Journal of human genetics · 2021Pooled it
- Three pleiotropic loci associated with bone mineral density and lean body mass.Molecular genetics and genomics : MGG · 2021Pooled it
- Inversed impaired osteogenic activity in children with severe obesity due to MC4R deficiency compared to LEP and LEPR deficiency.International journal of obesity (2005) · 2026Article
- Dual activation of MC3R and MC4R drives weight loss and reduces food intake in male primates with obesity.Nature communications · 2026Article
- Efficacy of GLP-1 analog peptides, semaglutide, tirzepatide, and retatrutide on MC4R deficient obesity and their comparison.International journal of obesity (2005) · 2026Article
- The melanocortin receptors as targets for general obesity: contextualizing clinical failures and analyzing future perspectives.Frontiers in endocrinology · 2026Review
- ADGRL1 is a glucose receptor involved in mediating energy and glucose homeostasis.Diabetologia · 2024Article
- Contrasting effects ofeLife · 2022Article
- Genetic differentiation in East African ethnicities and its relationship with endurance running success.PloS one · 2022Article
- MyD88 signalling is critical in the development of pancreatic cancer cachexia.Journal of cachexia, sarcopenia and muscle · 2019Article
- The role of GPCRs in bone diseases and dysfunctions.Bone research · 2019Review
- Pharmacological effect of human melanocortin-2 receptor accessory protein 2 variants on hypothalamic melanocortin receptors.Endocrine · 2018Article
- Activation of the central melanocortin system chronically reduces body mass without the necessity of long-term caloric restriction.Canadian journal of physiology and pharmacology · 2017Article
- Female Mice Lacking Estrogen Receptor-α in Hypothalamic Proopiomelanocortin (POMC) Neurons Display Enhanced Estrogenic Response on Cortical Bone Mass.Endocrinology · 2016Article
- Loss of Mrap2 is associated with Sim1 deficiency and increased circulating cholesterol.The Journal of endocrinology · 2016Article
- Bone and Muscle Pleiotropy: The Genetics of Associated Traits.Clinical reviews in bone and mineral metabolism · 2014Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Signaling via the type 4-melanocortin receptor (MC4R) is an important determinant of body weight in mice and humans, where loss of function mutations lead to significant obesity. Humans with mutations in the MC4R experience an increase in lean mass. However, the simultaneous accrual of fat mass in such individuals may contribute to this effect via mechanical loading. We therefore examined the relationship of fat mass and lean mass in mice lacking the type-4 melanocortin receptor (MC4RKO). We demonstrate that MC4RKO mice display increased lean body mass. Further, this is not dependent on changes in adipose mass, as MC4RKO mice possess more lean body mass than diet-induced obese (DIO) wild type mice with equivalent fat mass. To examine potential sources of the increased lean mass in MC4RKO mice, bone mass and strength were examined in MC4RKO mice. Both parameters increase with age in MC4RKO mice, which likely contributes to increases in lean body mass. We functionally characterized the increased lean mass in MC4RKO mice by examining their capacity for treadmill running. MC4R deficiency results in a decrease in exercise performance. No changes in the ratio of oxidative to glycolytic fibers were seen, however MC4RKO mice demonstrate a significantly reduced heart rate, which may underlie their impaired exercise performance. The reduced exercise capacity we report in the MC4RKO mouse has potential clinical ramifications, as efforts to control body weight in humans with melanocortin deficiency may be ineffective due to poor tolerance for physical activity.
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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.