Six other SNPs, rs2815752 (NEGR1), rs10938397 (GNPDA2), rs10838738 (MTCH2), rs7498665 (SH2B1), rs17782313 (MC4R) and rs11084753 (KCTD15), were not associated with obesity (P>0.05).
Most of these obesity disorders exhibit a distinct phenotype with varying degrees of hypothalamic and pituitary dysfunction and a recessive inheritance, whereas MC4-R mutation has a nonsyndromic phenotype with dominant inheritance.
Understanding the role natural products play, as well as the mechanisms behind their regulation of PPARγ activity is critical for future research into their therapeutic potential for fighting obesity.
Recently, Pomc knockout mice were generated and shown to develop hyperphagia and obesity with a time-course and severity comparable to MC4-R knockout mice, whereas daily administration of a stable alpha-melanocyte stimulating hormone analogue reversed this effect.
As the MC4R locus explains only 0.28% of the BMI and 0.14% of the WC phenotypic variance in the Scottish population, most of the genetic contribution to obesity remains to be identified.
In conclusion, this study confirmed and extended the previous findings, suggesting the MC4RV103I polymorphism is negatively associated with human obesity.
We further show that in the context of diet-induced obesityPPARγ-K107R-mutant mice have enhanced insulin sensitivity without the corresponding increase in adiposity that typically accompanies PPARγ activation by TZDs.
This modification of PPARgamma does not alter its adipogenic capacity, but leads to dysregulation of a large number of genes whose expression is altered in obesity, including a reduction in the expression of the insulin-sensitizing adipokine, adiponectin.
This review highlights the roles that PPARgamma play in the regulation of gene expression associated with normal cell physiology as well as the pathophysiology of multiple diseases including obesity, diabetes and cancer.
The fat mass and obesity-associated gene (FTO) rs9939609 and peroxisome proliferator-activated receptor gamma 2 gene (PPARG2) rs1801282 polymorphisms are type 2 diabetes mellitus susceptibility gene variants associated with obesity.
In our study, we addressed the hypothesis that a G-->A substitution at codon 103 (Val-103Ile) of the MC4R gene influences abdominal obesity, insulin, glucose, and lipid metabolism as well as circulating hormones, including salivary cortisol.
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).