Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Centre for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, China.
Institute for Metabolic Disease, Fengxian Central Hospital Affiliated to Southern Medical University, Shanghai, China.
Obes Surg. 2019 Apr;29(4):1169-1173. doi: 10.1007/s11695-018-03623-4.
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/m 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 (P = 0.001; P < 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.
减重手术作为肥胖症患者的最有效治疗选择正在兴起。下丘脑弓状核在代谢稳态中起重要作用。然而，与摄食中枢相关的突变对减重手术后体重减轻的影响仍不清楚。我们旨在通过全外显子组测序（WES）诊断单基因肥胖，并探讨单基因突变是否影响减重手术的效果。
我们收集了 2011 年 3 月至 2017 年 6 月期间在上海接受腹腔镜袖状胃切除术的年龄在 15 至 55 岁、BMI>28kg/m 的肥胖患者。收集了术前和术后与体重减轻和代谢特征相关的数据，包括空腹血糖（FBG）、高密度脂蛋白（HDL）胆固醇、低密度脂蛋白（LDL）胆固醇和甘油三酯。使用来自全血样本的基因组 DNA 在肥胖患者中进行 WES。
我们研究了 131 名肥胖成年人中高达 8.4%的一个突变的比例，然后评估了这些突变与体重减轻之间的关系。突变携带者在短期和长期内的体重减轻都较少。生存分析表明，突变携带者更难达到 20%体重减轻的目标（P=0.001；P<0.001），并且 Cox 回归模型仍显示差异具有统计学意义。两组患者术后 FBG、HDL 胆固醇和甘油三酯水平均有所改善，而两组之间存在显著差异。
我们的数据表明，8.4%的肥胖病例是由遗传变化引起的，突变对减重手术的效果有负面影响。
