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.
Furthermore, the P12APPARgamma polymorphism was not associated with obesity or WHR in the control population; it did not interact with energy intake or energy expenditure to alter risk of obesity or large WHR.
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).
Melanocortin-4 receptor gene (MC4R) variants are associated with obesity and binge eating disorder (BED), whereas the more prevalent proopiomelanocortin (POMC) and leptin receptor gene (LEPR) mutations are rarely associated with obesity or BED.
We focused on physical activity as an environmental risk factor, and on the GWA identified obesity variants in FTO (rs9939609) and near MC4R (rs17782313) as genetic risk factors.
Importantly, the results of the analysis of gene-diet interactions suggest that the allelic variants of candidate genes (leptin, TNFA, PPARG2) might strongly affect diet-related obesity risk.
We genotyped obesity risk single nucleotide polymorphisms (SNPs) derived from genome-wide association studies in or in proximity to the following genes: NEGR1, TNKS, SDCCAG8, FTO, MC4R, TMEM18, PTER, MTCH2, SH2B1, MAF, NPC1, and KCTD15.
Gly482Ser polymorphism in the peroxisome proliferator-activated receptor gamma coactivator-1alpha gene is associated with oxidative stress and abdominal obesity.
Humans with loss-of-function mutations in the melanocortin 4 receptor (MC4R) are an ideal group of subjects in whom the importance of melanocortin signalling in linking obesity to hypertension can be studied.
Interaction between Calpain 5, Peroxisome proliferator-activated receptor-gamma and Peroxisome proliferator-activated receptor-delta genes: a polygenic approach to obesity.
Phtalates are thought to contribute to obesity through their binding and activation of PPARγ receptor that in turn results in the upregulation of adipocyte production.
Nuclear receptors as targets for drug development: molecular mechanisms for regulation of obesity and insulin resistance by peroxisome proliferator-activated receptor gamma, CREB-binding protein, and adiponectin.
Our findings establish that common variants near MC4R influence fat mass, weight and obesity risk at the population level and reinforce the need for large-scale data integration to identify variants influencing continuous biomedical traits.