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.
These results conclude that the BGE extract containing several kinds of polymethoxy flavones showed PPARγ ligand-binding capacity in vitro and prevented obesity and insulin resistance independent of adiponectin secretion in mice.
VDR and PPARγ mRNA expression was higher in the adipose tissues of GDM women in comparison to that of women with normal glucose tolerance (VDR mRNA: G1 vs. N1: 210.00 [90.58-311.46] vs. 89.34 [63.74-159.92], G2 vs. N2: 298.67 [170.84-451.25] vs. 198.28 [119.46-261.23], PPARγ mRNA: G1 vs. N1: 100.72 [88.61-123.87] vs. 87.52 [66.37-100.04], G2 vs. N2: 117.33 [100.08-149.00] vs. 89.90 [76.95-109.09], P < 0.05), and their expression was the highest in GDM + overweight/obese women.