Leptin-Melanocortin pathway variants and gastric emptying in patients with obesity

BackgroundAccelerated gastric emptying (GE) is a trait seen in obesity. Mutations in the hypothalamic leptin-melanocortin 4 receptor (Leptin-MC4R) pathway have been associated with obesity. We sought to investigate the association of leptin-MC4R pathway variants and GE in patients with obesity.MethodsThis is a cross-sectional study of patients with a history of severe obesity that were genotyped and completed a GE test by scintigraphy. We evaluated the percentage of GE (GE %) at 2 and 4 h between both groups using ANCOVA with weight and sex as covariates. We subdivide patients into carriers based on the location of the identified variants (i.e., upstream or downstream of the Leptin-MC4R pathway) and compared them with noncarriers using ANOVA. Results are presented as mean and standard deviation (+/- SD).Key ResultsA total of 95 patients; nine carriers (67% females; 39.78 +/- 12.33 years; BMI: 49.14 +/- 12.96 kg/m2) and 86 noncarriers (87% female; 49.98 +/- 13.74 years; BMI: 40.75 +/- 6.29 kg/m2) were included. At 2 and 4 h, carriers had a delayed GE when compared noncarriers (p = 0.03 and p = 0.005, respectively). In carriers, when compared upstream carriers vs. downstream carriers vs. noncarriers by location there was a significant difference in GE among groups at 2 h and at 4 h (p = 0.02 and p = 0.01, respectively).Conclusions & InferencesCarriers of heterozygous variants in the Leptin-MC4R pathway had a delayed GE compared to noncarriers. These findings point the important relationship between the Leptin-MC4R pathway and gastric motility. Carriers of heterozygous variants in the leptin-melanocortin pathway exhibit delayed gastric emptying (GE) compared to noncarriers, indicating a potential link between genetic variations and altered gastric motility in obesity.image