An expanding set of severe obesity genetic defects are now identified that involve genes in the pathway that are either upstream of MC4R
-specifically, pro-opiomelanocortin (POMC) deficiency obesity, leptin receptor deficiency obesity, and likely Prader-Willi Syndrome (PWS)-or genes that are downstream of MC4R
or that affect MC4R
expression was higher in all slaughter weight phases, the relative expression in the fourth and fifth phase were significantly lower than in the first, second, and third phases (p<0.
We analysed MC4R
and MC3R for sequence variants that may contribute to the development of obesity in pupils from South Africa.
Twenty of the obese subjects with an MC4R
mutation were then matched by age, gender, and body mass index to 120 obese subjects without MC4R
While previous studies have shown that small activators of the molecule, which increase MC4R
activity, have the desirable effect of reducing food intake and insulin secretion from the pancreas (important to suppress the development of type 2 diabetes), it is not clear how, at the same time, they trigger the undesirable effect of increasing blood pressure.
Pharmaceutical companies are devising drugs that could provide proper signaling to combat obesity in people with mutations in the gene for MC4R
, Cone says.
In addition to the FTO and MC4R
genes already known, it was now possible for six more obesity genes to be identified: TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2, and NEGR1.
Associaion of MC4R
gene polymorphisms with growth and body composition traits in chicken.
which is developing the MC4R
peptide agonist, RM-493, for the treatment of obesity, including obesity caused by genetic deficiencies in the MC4 pathway such as Prader Willi Syndrome.
2004; 2006) suggested that single nucleotide polymorphisms (SNPs) of HMGA1 gene were significantly associated with fat deposition traits and polymorphisms between MC4R
(melanocortin 4 receptor) and HMGA1 were related to growth, fatness, and lean meat contents in commercial pigs.
The MC4 pathway is well validated in humans; loss-of-function mutations of MC4R
are associated with obesity and have a reported prevalence of 4%-6% in severe obesity.
Rhythm is developing the ghrelin peptide agonist, RM-131, for the treatment of diabetic gastroparesis and other GI functional disorders; and the MC4R
peptide agonist, RM-493, for obesity and diabetes.