17 patients with obesity-causing MC4R mutations (BMI: 35.5 ± 7.6) and 35 matched control participants with common obesity (BMI: 34.3 ± 7.1) underwent a DEXA scan for assessment of bone mineral density (BMD), bone mineral apparent density [BMAD = (BMD/√(bone area)], and bone turnover markers (BTMs).
We believe that our study may help to understand better the impact of MC4R gene on obesity development, and to help to provide personalized prevention/treatment strategies to fight against obesity and its metabolic consequences.
While most MC4R variants caused loss of function, a subset caused gain of function; these variants were associated with significantly lower BMI and lower odds of obesity, type 2 diabetes, and coronary artery disease.
Insights into the Allosteric Mechanism of Setmelanotide (RM-493) as a Potent and First-in-Class Melanocortin-4 Receptor (MC4R) Agonist To Treat Rare Genetic Disorders of Obesity through an in Silico Approach.
These data provide support for two hypotheses: (i) that the majority of these rare, obesity-associated mutations are likely defective and causative of obesity and (ii) that β-arrestin recruitment is a valuable marker of normal MC4R function.
Single SNP analysis showed that genetic variants in SLC30A10, TMEM18, GNPDA2, PRL, TFAP2B, BDNF, MTCH2, FTO, and MC4R were nominally associated with waist circumference (WC), BMI, and risk for abdominal or general obesity in the untreated patients with type 2 diabetes, as well as in the total group of patients with type 2 diabetes (untreated and treated) (p < 0.05).
When the melanocortin 4 receptor (MC4R) is knocked out globally, male mice display obesity, low sexual desire, and copulatory difficulties; however, it is unclear whether these phenotypes are interdependent.
In addition, BDNF rs6265 and MC4Rrs17782313 showed gender-dependent associations with decreased risk of having low HDL-C in males and increased risk of having abdominal obesity in females, respectively.
Melanocortin-4 receptor (<i>MC4R</i>) has been reported to be associated with the risk of obesity, and metabolically unhealthy obese (MUHO) patients tend to have a greater risk of cardiovascular complications than metabolically healthy obese (MHO) patients.