Grinbaum Ronit, Beglaibter Nahum, Mitrani-Rosenbaum Stella, Kaplan Lee M, Ben-Zvi Danny
Department of Surgery, Hadassah University Hospital Mount Scopus and the Hebrew University-Hadassah Medical School, Jerusalem 91240, Israel.
Goldyne Savad Institute of Gene Therapy, Hebrew University-Hadassah Medical School, Jerusalem 91120, Israel.
Metabolites. 2022 May 11;12(5):430. doi: 10.3390/metabo12050430.
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.
我们报告了一个特殊家庭中接受减肥手术的长期反应情况。该家庭中有四名患有严重肥胖症（体重指数为41 - 82kg/m²）的青少年，他们黑素皮质素4受体（MC4R）的C271R功能丧失突变呈纯合状态，还有三名成年人该突变呈杂合状态。所有患者具有相似的社会人口统计学背景，平均随访7年。四名纯合患者中有三名恢复了全部体重（体重指数为42 - 77kg/m²），而第四名患者体重减轻但仍肥胖，体重指数为60kg/m²。体重恢复与大多数合并症的复发相关，但高血糖未复发或延迟复发。纯合和杂合患者的糖化血红蛋白水平均有所降低。关于这一非常独特的基因背景的长期随访数据表明，减肥手术后体重减轻和肥胖改善需要活跃的MC4R信号传导，而血糖改善部分独立于体重减轻。该研究验证了动物模型，并证明了生物信号传导在体重调节中的重要性，即使在减肥手术后也是如此。
