Women with extreme obesity carrying rs17782313MC4R polymorphism present a higher pre-surgical BMI, are more unlikely to reach non-obesity BMI (<30 kg/m<sup>2</sup>) and tend to maintain a BMI > 35 kg/m<sup>2</sup> that characterize treatment failure.
Heterozygous loss-of-function MC4R mutations are the most common known genetic cause of monogenic human obesity, with more than 200 mutations described to date, affecting 2-3% of the population in various cohorts tested.
The artificial distinction between rare monogenic obesity and common polygenic obesity is now obsolete with the identification of MC4R variants of strong effect in the general population.
Thus, liraglutide induced an equal, clinically significant weight loss of 6% in both groups, indicating that the appetite-reducing effect of liraglutide is preserved in MC4R causal obesity and that liraglutide acts independently of the MC4R pathway.
We performed cross-species analysis to compare gene signatures of HCC from human patients and melanocortin 4 receptor-knockout mice, which develop HCC with obesity, insulin resistance, and dyslipidemia.
These results suggest that polymorphisms at LEP, LEPR, and MC4R may be useful biomarkers of obesity-related cardiometabolic alterations in our population.
To further define the MC4R pathway and its potential impact on obesity, we tested associations between body mass index (BMI) and LoF mutation burden in the POMC, PCSK1, and LEPR genes in various populations.
We investigated the associations between the obesity candidate genes (fat mass and obesity-associated (FTO), melanocortin-4 receptor (MC4R), leptin (LEP) and leptin receptor) and total energy intake and percentage of energy from macronutrients and ultra-processed foods before and during pregnancy.
We detected five rare heterozygous mutations in five different children with obesity: MC4Rp.Ile301Thr and SIM1 p.Val326Thrfs*43 mutations that were pathogenic; SIM1 p.Ser343Pro and SH2B1 p.Pro90His mutations that were likely pathogenic; and NTRK2 p.Leu140Phe that was of uncertain significance.
The importance of these neuropeptides in human energy balance is most powerfully illustrated by genetic forms of obesity that involve neuropeptides such as melanocortin-4-receptor (MC4R) deficiency.
The fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) genes have been consistently associated with the risk for obesity, but few studies have examined the association of the obesity risk alleles with gestational outcomes.
We aimed to determine the prevalence of melanocortin-4 receptor (MC4R) variants in a large German cohort of children with obesity in a pediatric outpatient clinic and to ascertain whether there is a specific phenotype associated with loss-of-function variants as previously reported.
Female mice heterozygous for Mc4r fed an obesogenic or a control diet for 5 weeks were mated with heterozygous males, with the same diet continued throughout pregnancy and lactation, generating four offspring groups: control wild type (C_wt), control knockout (C_KO), obese wild type (Ob_wt), and obese knockout (Ob_KO).
Obesity is a heritable disorder, and some of the many obesity susceptible genes are fat mass and obesity (FTO), leptin, and Melanocortin-4 receptor (MC4R).
Variants in the <i>MC4R</i> gene have been related to appetite and obesity.<b>Objective:</b> We aimed to examine whether weight-loss diets modified the effect of the "obesity-predisposing" <i>MC4R</i> genotype on appetite-related measures in a randomized controlled trial.<b>Methods:</b> A total of 811 overweight and obese subjects [25 ≤ body mass index (BMI; kg/m<sup>2</sup>) ≤ 40] aged 30-70 y were included in the 2-y POUNDS Lost (Preventing Overweight Using Novel Dietary Strategies) trial.
The objective of this study was to evaluate the influence of genetic variants related to obesity identified by genome-wide association studies (MC4R, TMEM18, KCTD15, SH2B1, SEC16B, BDNF, NEGR1, OLFM4 and HOXB5 genes) on anthropometric and dietary phenotypes in two Brazilian cohorts followed-up since birth.
Although the primary cause of obesity is unknown, there is significant effort to understand the role of the central melanocortin pathway in the brain as it has been shown that deficiency of proopiomelanocortin (POMC) [10,11] and melanocortin 4 receptors (MC4R) [12-15] in both rodents and humans results in severe hyperphagia and obesity [16-23].