Short-term Weight Trajectory of Severely Obese Individuals With and Without Pathogenic Satiety-Regulation Melanocortin 3/4 Receptor (MC3/4R) Mutations From a Multi-ethnic Asian Large Bariatric Surgery Program

• Main Authors: Joel Guanyi Lim GCE A-levels (Author), Angela Moh PhD (Author), Bhuvaneswari Pandian BSc (Author), Chalani Udhyami Ubeynarayana MSc (Author), Nathaniel Guanning Lim GCE A-levels (Author), Bo Chuan Tan MD, MRCS, MMed (Author), Deborah Ng MBBS, MRCS, MMed (Author), Tavintharan Subramaniam MBBS, MRCP, MCI (Author), Anton Cheng MBBS, FRACS (Author), Su Chi Lim MBBS, MRCP, PhD (Author)
• Format: Book
• Published: SAGE Publishing, 2023-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

The melanocortin (3 or 4) receptor (MC3/4R) is involved in regulating satiety and body weight. Therefore, pathogenic mutation in MC3/4R is associated with severe obesity, for which bariatric surgery is one of the treatment options. However, there is limited data on whether individuals with MC3/4R mutation will have differential weight response to surgery, especially among the Asian populations-the epi-center of the evolving global obesity epidemic. From our large prospective Obesity-Metabolism & Intervention Cohort Study (OMICS; N = 654, recruited between 2007 and 2022), 5 individuals with pathogenic MC3/4R mutations ("case") were identified using candidate-genes panel next-generation sequencing (Illumina iSeq). These subjects were carefully propensity score-matched (baseline body mass index [BMI], age, sex, ethnicity, proportion with diabetes, type of bariatric surgery) in a 1:4 ratio to other controls. We performed linear mixed model analysis (for repeated measurements) to compare their longitudinal weight trajectories (percentage total weight loss, %TWL) over 12 months. The 5 cases with MC3/4R mutations were 48 ± 11 years, BMI 40.8 ± 11.2 kg/m 2 , 60% with diabetes, and all males. Their weight at baseline (pre-op), and 6 months and 12 months after surgery were 120 ± 38, 100 ± 31, and 101 ± 30 kg, respectively. Compared with propensity score-matched controls (N = 20), linear mixed model analysis suggested no difference in surgically induced %TWL (β coefficient = −5.8 ± 3.7, P = .13) over 12 months between the groups. Therefore, we conclude that rare pathogenic MC3/4R mutations do not significantly modify weight change (%TWL) in response to bariatric surgery.

Item Description

2324-7096
10.1177/23247096231168108