Monogenic Obesity Mutations Lead to Less Weight Loss After Bariatric Surgery: a 6-Year Follow-Up Study
Bariatric surgery is emerging as the most effective treatment option for patients with obesity. Hypothalamic arcuate nucleus plays an important role in metabolic homeostasis. However, the influence of mutations related to the feeding center on weight loss after bariatric surgery is still unclear. We aimed to diagnose monogenic obesity by whole exome sequencing (WES) and explore whether monogenic mutations influence the effectiveness of bariatric surgery.
We collected obese patients aged 15 to 55 with a BMI > 28 kg/m2 and who underwent laparoscopic sleeve gastrectomy from March 2011 to June 2017 in Shanghai. Data related to weight loss and metabolic characteristics preoperatively and postoperatively were collected, including fasting blood glucose (FBG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides. WES was performed in obese patients using genomic DNA from whole blood samples.
We investigated the proportion of 131 obese adults with one mutation as high as to 8.4% and then evaluated the association between these mutations and weight loss. Mutation carriers had less weight loss over both short-term and long-term periods. Survival analyses indicated it was harder to attain the goal of 20% weight loss for mutation carriers (Plog-rank = 0.001; Pbreslow < 0.001), and the difference remained significant with a Cox regression model. Improvement in FBG, HDL cholesterol, and triglyceride levels postoperatively was observed in both groups, while there were significant differences between the two groups.
Our data indicated that 8.4% of obesity cases were caused by change in genetics, and mutations had negative effects on the efficacy of bariatric surgery.
KeywordsMonogenic obesity Bariatric surgery Weight loss Mutations Whole exome sequencing
This work is supported by the National Key Research and Development Program of China (2016YFA0502003), the National Natural Science Foundation of China (81570713), the National Key Research and Development Program (2016YFC0903303), the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20152527), the Outstanding Academic Leaders of Shanghai Health System (2017BR008), and the Yangtze River Scholar.
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Informed consent was obtained from all participants.
Human and Animal Rights
The study was performed in accord with the ethical standards of the Declaration of Helsinki.