The Obesogenic and Glycemic Effect of Bariatric Surgery in a Family with a Melanocortin 4 Receptor Loss-of-Function Mutation

We report the long-term response to bariatric surgery in a singular family of four adolescents with severe obesity (41-82 kg/m ), homozygous for the C271R loss-of-function mutation in the melanocortin 4 receptor (MC4R), and three adults heterozygous for the same mutation. All patients had similar so...

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Published in:Metabolites 2022-05, Vol.12 (5), p.430
Main Authors: Grinbaum, Ronit, Beglaibter, Nahum, Mitrani-Rosenbaum, Stella, Kaplan, Lee M, Ben-Zvi, Danny
Format: Article
Language:English
Subjects:
Animal models
bariatric surgery
Blood glucose
Body mass index
Body weight loss
Case Report
diabetes
Gastrointestinal surgery
Hyperglycemia
Melanocortin
melanocortin 4 receptor
Melanocortin MC4 receptors
Mutation
Obesity
OSA
Patients
Surgery
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Summary:We report the long-term response to bariatric surgery in a singular family of four adolescents with severe obesity (41-82 kg/m ), homozygous for the C271R loss-of-function mutation in the melanocortin 4 receptor (MC4R), and three adults heterozygous for the same mutation. All patients had similar sociodemographic backgrounds and were followed for an average of 7 years. Three of the four homozygous patients regained their full weight (42-77 kg/m ), while the fourth lost weight but remained obese with a body mass index of 60 kg/m . Weight regain was associated with relapse of most comorbidities, yet hyperglycemia did not relapse or was delayed. A1c levels were reduced in homozygous and heterozygous patients. The long-term follow-up data on this very unique genetic setting show that weight loss and amelioration of obesity following bariatric surgery require active MC4R signaling, while the improvement in glycemia is in part independent of weight loss. The study validates animal models and demonstrates the importance of biological signaling in the regulation of weight, even after bariatric surgery.
ISSN:2218-1989
2218-1989
DOI:10.3390/metabo12050430