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MRAP2b decreases the constitutive activity of the MC4R during fasting periods, driving the animal toward a positive energy balance.
MRAP2 proteins allow for developmental control of MC4R activity, with MRAP2a blocking its function and stimulating growth during larval development, whereas MRAP2b enhances responsiveness to alpha-MSH once the zebrafish begins feeding, thus increasing the capacity for regulated feeding and growth.
MC4R haploinsufficiency clearly segregates with higher BMI; however, severe obesity is not fully penetrant even in MC4R LOF carriers, suggesting critical roles for environmental and lifestyle factors in MC4R monogenic obesity.
there are associations between FTO-rs9939609, MC4R-rs17782313 and LEP-rs7799039 genes and the components of dietary intake in pregnant women
We detected one rare MC4R mutation leading to partially reduced MC4R function, previously detected in individuals of normal height. Hence, a major relevance of this variant for SNS is unlikely. The detected MC4R polymorphism p.Val103Ile was nominally associated with SNS.
The combined effect of polymorphisms in FTO and MC4 receptor genes on the risk of obesity in children and adolescents northwest China are reported.
Methylation statuses of MC4R and HNF4alpha in cord blood were significantly decreased, whereas childhood body mass index was significantly increased, in children with high triglyceride levels compared with children with low triglyceride levels. Epigenetic modifications occurring in early life may contribute to subsequent metabolic-related disorders.
Studied possibility of using pediatric body mass index as a biomarker for obesity due to leptin, leptin receptor, and melanocortin 4 receptor (MC4R) deficiency. Data showed that early childhood BMI is useful in distinguishing between patients with a functional relevant homozygous or compound heterozygous mutation in leptin or leptin receptor gene from patients with a heterozygous mutations in MC4R gene.
Seven MC4R gene variants were identified in the heterozygous state in 21 patients.Both in silico and family segregation analysis confirm the correlation between novel identified mutations in MC4R gene and obesity development. The correlation between the four variants (c.-24G>A, p.Thr101Ile, p.Ala259Asp and p.Ser30Phe) and the obesity phenotype allows the conclusion that all of the four mutations cause a monogenic obesity.
Impaired signaling from the primary cilia of MC4R neurons is a common pathway underlying genetic causes of obesity in humans. MC4R colocalizes with ADCY3 at the primary cilia of a subset of hypothalamic neurons; obesity-associated MC4R mutations impair ciliary localization and inhibition of adenylyl cyclase signaling at the primary cilia of these neurons increases body weight.
The MC4R variant rs6567160 was associated with greater postpartum increase of HbA1c (beta = 0.08%; P = 0.03) and 2-hour oral glucose tolerance test glucose concentrations (beta = 0.25 mmol/L; P = 0.02). In addition, the authors found an interaction between the MC4R genotype and postpartum weight reduction on changes in fasting plasma glucose (P-interaction = 0.03).
MC4R mutation homozygotes exhibited morbid early-onset obesity.
Association between MC4R single nucleoitde polymorphisms (rs17782313, rs10871777, rs12970134, rs17700144) and overweight/obesity in Chinese Han adolescents.
Determined the potential of AgRP to regulate the activation of intracellular kinases, including extracellular signal-regulated kinase 1 and 2 (ERK1/2), AKT and AMP-activated protein kinase (AMPK), through neural MC3R and MC4R.
We showed that MC4R rs17782313 and FTO rs9939609 were positively associated with zBMI, with weak and very weak effects, respectively, suggesting a very scarce contribution to childhood obesity.
These findings show that MC4R methylation status in the blood of children is associated with metabolic profiles. Therefore, we suggest that the DNA methylation status might serve as a potential epigenetic biomarkers of metabolic syndrome.
This study suggests that the MC4R AA genotype is significantly associated with a shorter progression-free and overall survival in glioblastoma patients treated with radiotherapy and temozolomide.
This review is devoted to anatomic distribution of MC4R in the brain and interaction between MC4R and other pathways for pain modulation.
Results show that MC4R rs17782313 allele C was associated with higher HDL cholesterol and also showed a marginal contribution to reduced risk of MetS. These finding suggest that MC4R genetic variant may be useful biomarker of cardiometabolic risk in obese patients.
Genotyping for the near MC4R polymorphism, rs17782313 revealed an association with moderately obese patients
The polymorphism of FTO gene rs17817449 and GNB3 gene rs5443 (C825T) may be a genetic determinant of obesity in Saudi population whereas impact of MC4R Asn274Ser change could not be detected.
central melanocortin signalling has an effect on fat and sucrose preference in humans
investigated the role of melanocortin 4 receptors (MC4Rs) in aversive processing using genetically modified mice and a behavioral test in which mice avoid an environment that they have learned to associate with aversive stimuli
MC4R interacted with GRP78 in both the cytosol and at the cell surface
Low MC4R expression is associated with obesity with increased food intake and decreased energy expenditure, along with impaired insulin sensitivity and cold-induced thermogenesis.
Mc4r and Drd1a can serve as surrogate odorant receptors in mouse olfactory sensory neurons
Mc4r knockout offspring showed higher body, liver and adipose tissue weights; and mild hepatic steatosis
vertebrate limb regeneration with Mc4r-mediated energy homeostasis and provide a new avenue for understanding Mc4r signaling in the peripheral organs
Together this study identifies MC4R deletion as a novel and potentially clinically important cause of dilated cardiomyopathy and heart failure.
Data suggest that central melanocortin-4 receptor (MC4-R) and tryptophan hydroxylase (TPH) are involved in the efferent neuronal control of the kidneys.
Data (including data from studies in knockout mice) suggest that expression of Mc4r in Sim1 neurons of arcuate nucleus of hypothalamus, paraventricular hypothalamic nucleus, and amygdala is involved in sexual function; here, expression of Mc4r only on Sim1 neurons reverses sexual deficits seen in Mc4r null mice. (Mc4r = melanocortin 4 receptor; Sim1 = single-minded homolog 1)
Thus, Mc4r in the PVH appears to be required for early-life programming of hypertension arising from either maternal obesity or neonatal hyperleptinemia. Early-life exposure of the PVH to maternal obesity through postnatal elevation of leptin may have long-term consequences for cardiovascular health.
disruption of this hippocampal POMC/MC4R circuit might contribute to synaptic dysfunction observed in Alzheimer's disease.
Study shows that melanocortin 4 receptor constitutive activity chronically inhibits specific subtypes of neuronal voltage-gated calcium channels.
Loss of MC4R is associated with hepatic steatosis.
The data suggest that lipid stress disrupts steps of endocytosis following MC4R localization to clathrin-coated sites and exclusion of the receptor from the extracellular medium.
Confirmation of the impairment of GH-IGF-1 release in hyperphagic MC4R KO mice suggests a role for insulin in regulating both the release of GH, but also in mediating growth during periods of physiologically suppressed GH-IGF-1 levels
Loss of Mc4r expression is associated with non-alcoholic fatty liver disease.
results identify lipocalin 2 as a bone-derived hormone with metabolic regulatory effects, which suppresses appetite in a MC4R-dependent manner, and show that the control of appetite is an endocrine function of bone
Atherosclerosis and Hypercholesterolemia in Mice Lacking Both the Melanocortin Type 4 Receptor and Low Density Lipoprotein Receptor
results indicate that the MC4R is not required for estrogen's effects on metabolic and reproductive functions
Mc4r receptor expression in the cuneiform nucleus is involved in modulation of opioidergic signaling.
evaluate the association of single nucleotide polymorphisms (SNPs) in MC4R with milk production traits in water buffalo. Based on the SNP data, seven haplotypes were constructed. Three SNPs H1 (AGT), H2 (GAT), and H3 (GAC) accounted for 93.0% of the total individuals. Statistical analysis indicated that the SNP g.1104C>T was significantly associated with milk yield, protein, and fat percentage.
The MC4R gene may thus be a candidate gene for carcass traits with MC4R single nucleotide polymorphisms being potentially valuable as genetic markers for economic traits in Hanwoo.
The aim was to estimate the frequency of the SNPs in the MC4R gene and to determine if individual genotypes were associated with several economic traits.
The results suggested that -129A>G and 1,069C>G single nucleotide polymorphism of the MC4R gene may be useful as a genetic marker for carcass and meat quality traits in Qinchuan cattle.
results are suggestive that adrenal glucocorticoid production could be regulated through melanocortin 4 receptor
Single nucleotide polymorphisms in 5'-untranslated region of MC4R gene, were detected.
These results indicate that genetic selection against boar taint is possible using MC4R as a marker.
These results suggest that LEPR, MC4R, PIK3C3 and VRTN are useful markers for accurately predicting breeding values in Duroc pigs.
Transcriptional profiling was used to identify genes and pathways that responded to intracerebroventricular injection of MC4R agonist [Nle(4), d-Phe(7)]-alpha-melanocyte stimulating hormone in pigs homozygous for the missense mutation in the MC4R.
study did not find any significant associations for polymorphisms in insulin-like grwoth factor 2, GTP Binding Protein alpha Subunits, Gs and melanocortin receptor 4 genes with reproductive traits of Polish Landrace and Large White pigs
Linkage disequilibrium analysis among MC4R, LEP and H-FABP revealed that these genes were independent.
The c.1426G>A polymorphism affects daily gain, feed conversion ratio and ham weight in both breeds, lean cuts in the Italian Duroc and backfat thickness in the Italian Large White.
MC4R allelic variants had no effects on meat quality traits.
The effects of missense mutations of MC4R on carcass composition, growth traits and meat quality in 1191 gilts of five swine breeds are reported.
No effect of the MC4R trait nucleotides could be seen on muscle growth.
Results of associated analysis show that the polymorphism of MC4R gene was associated traits of back fat thickness (BF).
A polymorphism within the MC4R gene is associated with feed intake and increased growth.
A polymorphism within the MC4R gene is associated with the fat/meat ratio.
Characterization of polymorphisms in the MC4R gene in relation to growth and fat deposition.
pMC4R mutants D298N and R236H do not have any overt functional defects.
sequenced MC4R genes in 72 pigs belonging to lean (Large White and Duroc), fat (Meishan and Casertana) breeds and also Wild Boar
The protein encoded by this gene is a membrane-bound receptor and member of the melanocortin receptor family. The encoded protein interacts with adrenocorticotropic and MSH hormones and is mediated by G proteins. This is an intronless gene. Defects in this gene are a cause of autosomal dominant obesity.
melanocortin receptor 4
, melanocortin 4-receptor
, melanocortin 4 receptor
, melanocortin-4 receptor
, Melanocortin receptor 4