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

• Published in: Neurogastroenterology and motility 2024-05, Vol.36 (5), p.e14764-n/a
• Main Authors: Cifuentes, Lizeth, Ghusn, Wissam, Campos, Alejandro, Bublitz, Joshua T., Hurtado, Maria Daniela, Olson, Janet, Acosta, Andres
• Format: Article
• Language: English
• Subjects: accelerated gastric emptying; Gastric emptying; Gastric motility; Hypothalamus; Leptin; leptin‐MC4R pathway; Melanocortin; Melanocortin MC4 receptors; Obesity; Scintigraphy
• ISSN: 1350-1925; 1365-2982
• DOI: 10.1111/nmo.14764

Background Accelerated 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. Methods This 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 Results A 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 & Inferences Carriers 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.