Atkin Stephen L, Ramachandran Vimal, Yousri Noha A, Benurwar Manasi, Simper Steven C, McKinlay Rodrick, Adams Ted D, Najafi-Shoushtari S Hani, Hunt Steven C
Department of Medicine, Weill Cornell Medicine, Doha, Qatar.
Department of Cell and Developmental Biology, Weill Cornell Medicine, Doha, Qatar.
Front Endocrinol (Lausanne). 2019 Jan 4;9:773. doi: 10.3389/fendo.2018.00773. eCollection 2018.
Early metabolic responses following bariatric surgery appear greater than expected given the initial weight loss and coincide with improvement in diabetes. We hypothesized that small non-coding microRNA changes might contribute to regulating mechanisms for metabolic changes and weight loss in patients with severe obesity and diabetes. Twenty-nine type 2 patients with severe obesity (mean BMI 46.2 kg/m) and diabetes underwent Roux-en-Y gastric bypass (RYGB) surgery. Clinical measurements and fasting blood samples were taken preoperatively and at day 21 postoperatively. Normalization of fasting glucose and HbA1c following bariatric surgery (short-term diabetes remission) was defined as withdrawal of anti-diabetic medication and fasting glucose < 100 mg/dL (5.6 mmol/L) or HbA1c < 6.0%. MicroRNA expression was determined by quantitative polymerase chain reaction and tested for significant changes after surgery. BMI decreased by 3.8 kg/m 21 days postoperatively. Eighteen of 29 RYGB (62%) had short-term diabetes remission. Changes from pre- to post-surgery in 32 of 175 microRNAs were nominally significant ( < 0.05). Following multiple comparison adjustment, changes in seven microRNAs remained significant: miR-7-5p, let-7f-5p, miR-15b-5p, let-7i-5p, miR-320c, miR-205-5p, and miR-335-5p. Four pathways were over-represented by these seven microRNAs, including diabetes and insulin resistance pathways. Seven microRNAs showed significant changes 21 days after bariatric surgery. Functional pathways of the altered microRNAs were associated with diabetes-, pituitary-, and liver-related disease, with expression in natural killer cells, and pivotal intestinal pathology suggesting possible mechanistic roles in early diabetes responses following bariatric surgery.
考虑到初始体重减轻情况，减肥手术后的早期代谢反应似乎比预期的更大，且与糖尿病病情改善同时出现。我们推测，小非编码微小RNA的变化可能有助于调节重度肥胖和糖尿病患者的代谢变化及体重减轻机制。29例重度肥胖（平均BMI为46.2kg/m²）的2型糖尿病患者接受了 Roux-en-Y 胃旁路术（RYGB）。术前及术后第21天进行临床测量和空腹血样采集。减肥手术后空腹血糖和糖化血红蛋白的正常化（短期糖尿病缓解）定义为停用抗糖尿病药物且空腹血糖<100mg/dL（5.6mmol/L）或糖化血红蛋白<6.0%。通过定量聚合酶链反应测定微小RNA表达，并检测术后的显著变化。术后21天BMI下降了3.8kg/m²。29例接受RYGB手术的患者中有18例（62%）实现了短期糖尿病缓解。175种微小RNA中有32种术后发生的变化具有名义显著性（P<0.05）。经过多重比较校正后，7种微小RNA的变化仍具有显著性：miR-7-5p、let-7f-5p、miR-15b-5p、let-7i-5p、miR-320c、miR-205-5p和miR-335-5p。这7种微小RNA在4条通路中过度富集，包括糖尿病和胰岛素抵抗通路。减肥手术后21天，7种微小RNA出现显著变化。这些改变的微小RNA的功能通路与糖尿病、垂体和肝脏相关疾病有关，在自然杀伤细胞中有表达，且关键的肠道病理表明它们在减肥手术后早期糖尿病反应中可能发挥机制性作用。
