Liu Qiaoran, Wang Shuo, Wei Meng, Huang Xin, Cheng Yugang, Shao Yi, Xia Pingtian, Zhong Mingwei, Liu Shaozhuang, Zhang Guangyong, Hu Sanyuan
Department of General Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China.
Front Endocrinol (Lausanne). 2019 Aug 30;10:566. doi: 10.3389/fendo.2019.00566. eCollection 2019.
Bariatric surgery can profoundly improve glucose and lipid metabolism in diabetic rats. Fibroblast growth factor 21 (FGF21) is an important hormone with multiple metabolic beneficial effects. Alteration in serum FGF21 level after bariatric surgery has been reported with conflicting results. Here, we investigated the effect of bariatric surgeries on FGF21 expression and sensitivity. We performed duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG) and sham surgery in diabetic rats induced by high fat diet and streptozotocin. Metabolic parameters, including body weight, food intake, glucose tolerance, and lipid profiles, were monitored. FGF21 levels in both serum and liver were measured after surgery. FGF21 signaling pathway including FGF receptor 1 (FGFR1), β-klotho (KLB), and phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) was detected in the liver and white adipose tissue (WAT). We also determined FGF21 sensitivity post-operatively by acute recombinant human FGF21 injection. Oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were conducted immediately after FGF21 injection. Serum triglyceride (TG) and non-esterified fatty acid (NEFA) were measured and the mRNA levels of early growth response 1 (Egr1) and c-Fos in the liver and WAT were detected after FGF21 injection. Improvements in glucose tolerance, insulin sensitivity, and lipid profiles were observed after bariatric surgeries along with ameliorated lipid metabolism in the liver and WAT. Serum and hepatic FGF21 levels decreased in both DJB and SG groups. FGFR1 and phosphorylated ERK1/2 levels increased in both DJB and SG groups 8 weeks after surgery. The expression of KLB was downregulated only in the WAT after DJB and SG. Significant alteration of OGTT and ITT were observed after acute FGF21 administration in DJB and SG groups. Serum TG and NEFA in DJB and SG groups also decreased after FGF21 administration. And increased mRNA levels of Egr1 and c-Fos were detected in the liver and WAT after DJB and SG surgeries. DJB and SG surgeries can downregulate hepatic expression of FGF21, restore FGF21 signaling pathway and improve FGF21 sensitivity in high-fat diet/streptozotocin-induced diabetic rats.
减肥手术可显著改善糖尿病大鼠的糖代谢和脂代谢。成纤维细胞生长因子21（FGF21）是一种具有多种代谢有益作用的重要激素。有报道称减肥手术后血清FGF21水平的变化结果相互矛盾。在此，我们研究了减肥手术对FGF21表达和敏感性的影响。我们对高脂饮食和链脲佐菌素诱导的糖尿病大鼠进行十二指肠空肠旁路术（DJB）、袖状胃切除术（SG）和假手术。监测包括体重、食物摄入量、葡萄糖耐量和血脂谱在内的代谢参数。术后测量血清和肝脏中的FGF21水平。在肝脏和白色脂肪组织（WAT）中检测FGF21信号通路，包括FGF受体1（FGFR1）、β-klotho（KLB）和磷酸化细胞外信号调节激酶1/2（ERK1/2）。我们还通过急性注射重组人FGF21来测定术后FGF21的敏感性。在注射FGF21后立即进行口服葡萄糖耐量试验（OGTT）和胰岛素耐量试验（ITT）。测量血清甘油三酯（TG）和非酯化脂肪酸（NEFA），并在注射FGF21后检测肝脏和WAT中早期生长反应1（Egr1）和c-Fos的mRNA水平。减肥手术后观察到葡萄糖耐量、胰岛素敏感性和血脂谱得到改善，同时肝脏和WAT中的脂质代谢也得到改善。DJB组和SG组的血清和肝脏FGF21水平均降低。术后8周，DJB组和SG组的FGFR1和磷酸化ERK1/2水平均升高。DJB和SG术后仅WAT中的KLB表达下调。在DJB组和SG组急性给予FGF21后，观察到OGTT和ITT有显著变化。给予FGF21后，DJB组和SG组的血清TG和NEFA也降低。DJB和SG手术后，在肝脏和WAT中检测到Egr1和c-Fos的mRNA水平升高。DJB和SG手术可下调高脂饮食/链脲佐菌素诱导的糖尿病大鼠肝脏中FGF21的表达，恢复FGF21信号通路并提高FGF21敏感性。
