Sima Fansa, MD1, Wissam Ghusn, MD1, Diego Anazco, MD1, Elif Tama, MD2, Maria Daniela. Hurtado, MD, PhD2, Andres Acosta, MD, PhD1 1Mayo Clinic, Rochester, MN; 2Mayo Clinic, Jacksonville, FL
Introduction: Heterozygous genetic variants in the leptin-melanocortin pathway (LMP) have been associated with obesity. LMP play a role in food intake regulation. Pathophysiological and behavioral obesity-related phenotypic traits have not been clearly defined in patients with obesity and LMP variants.
Methods: This is a retrospective cohort study from adult participants who have undergone genetic testing and phenotype classification for obesity. Analysis was divided by 1) patients who had a genetic mutation (“carriers” group), and 2) patients who had no genetic mutation (“non-carriers” group). Our primary endpoint was the number of calories consumed during an ad libitum buffet meal. Secondary end points included comparison of phenotype-defining variables (gastric emptying [GE], resting energy expenditure% [REE%], and HADS-A score). Analysis was done using Mann-Whitney test for continuous data. Results are reported as mean ± standard deviation (SD).
Results: In a total of 25 patients. 9 patients were carriers (77.8% female, age 37.0±8.4 years, body-mass index [BMI] 44.8±7.1 kg/m2) and 16 patients were non-carriers (94% female, age 44.9±10.7 years, BMI 43.2±3.9 kg/m2) of a LMP variant. There were no significant differences in baseline characteristics. The carriers consumed more calories at the ad libitum buffet meal (1094.3 ± 395.6) compared to the non-carriers group (774.8 ± 265.0, p=0.04). The most common genetic mutation was PCSK1 (n=5), and those patients consumed an average of 1261.0 ± 469.9 kcal, the highest reported value among all genetic variants. There were no significant differences between GE (p=0.97), REE% (p=0.56) and HADS-A (p=0.43) score among the groups.
Discussion: Carriers of heterozygous variants in the LMP consumed more calories prior to reaching fullness at the ad libitum buffet meal than non-carriers. These findings suggest a key role of the LMP in abnormal satiation.
Disclosures:
Sima Fansa indicated no relevant financial relationships.
Wissam Ghusn indicated no relevant financial relationships.
Diego Anazco indicated no relevant financial relationships.
Elif Tama indicated no relevant financial relationships.
Maria Hurtado indicated no relevant financial relationships.
Andres Acosta: Amgen Pharmaceuticals – Consultant. General Mills – Consultant. Gila Therapeutics – Stock-privately held company. Phenomix Sciences – Stock-privately held company. Rhythm Pharmaceuticals – Consultant.
Sima Fansa, MD1, Wissam Ghusn, MD1, Diego Anazco, MD1, Elif Tama, MD2, Maria Daniela. Hurtado, MD, PhD2, Andres Acosta, MD, PhD1. P2616 - Association of Leptin-Melanocortin Pathway Genetic Variants and Obesity-Related Phenotypic Traits, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.
