ArticleObesity (Silver Spring, Md.)2012
Melanocortin receptor 4 deficiency affects body weight regulation, grooming behavior, and substrate preference in the rat.
Article in Obesity (Silver Spring, Md.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 98 citations in OpenAlex.
- Melanocortin 4 receptor agonism enhances sexual brain processing in women with hypoactive sexual desire disorder.The Journal of clinical investigation · 2022Trial
- Maternal monosaccharide diets modulate melanocortin-4 receptor signaling and metabolic state in rat offspring.Pharmacological reports : PR · 2025Article
- Understanding food addiction in obesity: a genetic perspective.Journal of eating disorders · 2025Article
- From Mother to Child: Epigenetic Signatures of Hyperglycemia and Obesity during Pregnancy.Nutrients · 2024Article
- Motivational dysregulation with melanocortin 4 receptor haploinsufficiency.NeuroImmune pharmacology and therapeutics · 2024Article
- A molecularly defined orbitofrontal cortical neuron population controls compulsive-like behavior, but not inflexible choice or habit.Progress in neurobiology · 2024Article
- Shank3 deficiency elicits autistic-like behaviors by activating p38α in hypothalamic AgRP neurons.Molecular autism · 2024Article
- Genome-wide association studies of human and rat BMI converge on synapse, epigenome, and hormone signaling networks.Cell reports · 2023Article
- Reduced contextually induced muscle thermogenesis in rats with calorie restriction and lower aerobic fitness but not monogenic obesity.Temperature (Austin, Tex.) · 2023Article
- Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications.Physiological reviews · 2021Review
- Cellular and Molecular Players in the Interplay between Adipose Tissue and Breast Cancer.International journal of molecular sciences · 2021Review
- Review
- Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.Journal of biomedical science · 2020Review
- Long-term effects of pro-opiomelanocortin methylation induced in food-restricted dams on metabolic phenotypes in male rat offspring.Obstetrics & gynecology science · 2020Article
- A systematic review on different models of inducing obesity in animals: Advantages and limitations.Journal of advanced veterinary and animal research · 2020Review
- Sex-dependent effects of MC4R genotype on HPA axis tone: implications for stress-associated cardiometabolic disease.Stress (Amsterdam, Netherlands) · 2019Article
- Melanotan-II reverses autistic features in a maternal immune activation mouse model of autism.PloS one · 2019Article
- Melanocortin-4 Receptor Deficiency Attenuates Placental Ischemia-Induced Hypertension in Pregnant Rats.Hypertension (Dallas, Tex. : 1979) · 2019Article
- Melanocortin Receptor 4 Signaling Regulates Vertebrate Limb Regeneration.Developmental cell · 2018Article
- Genetic variants help define the role of the MC4R C-terminus in signaling and cell surface stability.Scientific reports · 2018Article
Corrections and comments
- Erratum issuedDosage error in article text
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Obesity is caused by an imbalance between energy intake and expenditure and has become a major health-care problem in western society. The central melanocortin system plays a crucial role in the regulation of feeding and energy expenditure, and functional loss of melanocortin receptor 4 (MC4R) is the most common genetic cause of human obesity. In this study, we present the first functional Mc4r knockout model in the rat, resulting from an N-ethyl-N-nitrosourea mutagenesis-induced point mutation. In vitro observations revealed impaired membrane-binding and subsequent nonfunctionality of the receptor, whereas in vivo observations showed that functional loss of MC4R increased body weight, food intake, white adipose mass, and changed substrate preference. In addition, intracerebroventricular (ICV) administration of Agouti-Related Protein(79-129) (AgRP(79-129)), an MC4R inverse agonist, or Melanotan-II (MTII), an MC4R agonist, did affect feeding behavior in wild-type rats but not in homozygous mutant rats, confirming complete loss of MC4R function in vivo. Finally, ICV administration of MTII induced excessive grooming behavior in wild-type rats, whereas this effect was absent in homozygous mutant rats, indicating that MTII-induced grooming behavior is exclusively regulated via MC4R pathways. Taken together, we expect that the MC4R rat model described here will be a valuable tool for studying monogenic obesity in humans. More specifically, the relative big size and increased cognitive capacity of rats as compared to mice will facilitate complex behavioral studies and detailed mechanistic studies regarding central function of MC4R, both of which ultimately may help to further understand the specific mechanisms that induce obesity during loss of MC4R function.
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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.