Yan Kemin, Chen Weijie, Zhu Huijuan, Lin Guole, Pan Hui, Li Naishi, Wang Linjie, Yang Hongbo, Liu Meijuan, Gong Fengying
Key Laboratory of Endocrinology of National Health and Family Planning Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China.
Front Physiol. 2018 Mar 9;9:191. doi: 10.3389/fphys.2018.00191. eCollection 2018.
Ileal transposition (IT) surgery has been reported to improve glucose and lipid metabolism, and fibroblast growth factor 21 (FGF21) is a powerful metabolic regulator. In the present study, we aimed to investigate the effects of IT surgery on metabolism and its possible relationship with the FGF21 signaling pathway in diabetic Goto-Kakizaki (GK) rats. Ten-week-old male GK rats were subjected to IT surgery with translocation of a 10 cm ileal segment to the proximal jejunum (IT group) or sham surgery without the ileum transposition (Sham-IT group). Rats in the no surgery group did not receive any surgical intervention. Six weeks later, body weight, fat mass, fasting blood glucose (FBG), and serum levels of FGF21 and leptin were measured. The expression of the FGF21 signaling pathway and white adipose tissue (WAT) browning-related genes in the WAT and liver were evaluated by real-time reverse transcription polymerase chain reaction (RT-qPCR) and western blot. IT surgery significantly decreased the body weights and FBG levels and increased the insulin sensitivity of GK rats. The total WAT mass of the IT rats showed a 41.5% reduction compared with the Sham-IT rats, and serum levels of FGF21 and leptin of the IT rats decreased by 26.3 and 61.7%, respectively (all < 0.05). The mRNA levels of fibroblast growth factor receptor 1 (FGFR1) and its co-receptor β klotho (KLB) in the perirenal WAT (pWAT) of the IT rats were 1.4- and 2.4-fold that of the Sham-IT rats, respectively, and the FGFR1 protein levels were 1.7-fold of the Sham-IT rats (all < 0.05). In accordance with the pWAT, the protein levels of FGFR1 and KLB in the epididymal WAT (eWAT) of the IT rats notably increased to 3.0- and 3.9-fold of the Sham-IT rats ( < 0.05). Furthermore, uncoupling protein 1 (UCP1) protein levels in the eWAT and pWAT of the IT rats also increased to 2.2- and 2.3-fold of the Sham-IT rats ( < 0.05). However, the protein levels of FGFR1 and KLB in the subcutaneous WAT (sWAT) of the IT rats decreased by 34.4 and 72.1%, respectively, compared with the Sham-IT rats ( < 0.05). In addition, the protein levels of FGF21 and KLB in the livers of IT rats were 3.9- and 2.3-fold of the Sham-IT rats (all < 0.05). IT surgery significantly decreased fat mass and improved glucose metabolism in diabetic GK rats. These beneficial roles of IT surgery were probably associated with its stimulatory action on the expression of FGFR1 and KLB in both the eWAT and the pWAT, thereby promoting UCP1 expression in these tissues.
据报道，回肠转位（IT）手术可改善葡萄糖和脂质代谢，而成纤维细胞生长因子21（FGF21）是一种强大的代谢调节因子。在本研究中，我们旨在探讨IT手术对糖尿病Goto-Kakizaki（GK）大鼠代谢的影响及其与FGF21信号通路的可能关系。将10周龄雄性GK大鼠进行IT手术，将10 cm回肠段移位至空肠近端（IT组）或进行不进行回肠转位的假手术（假IT组）。未手术组大鼠未接受任何手术干预。六周后，测量体重、脂肪量、空腹血糖（FBG）以及FGF21和瘦素的血清水平。通过实时逆转录聚合酶链反应（RT-qPCR）和蛋白质印迹法评估WAT和肝脏中FGF21信号通路及白色脂肪组织（WAT）褐变相关基因的表达。IT手术显著降低了GK大鼠的体重和FBG水平，并提高了其胰岛素敏感性。与假IT大鼠相比，IT大鼠的总WAT质量降低了41.5%，IT大鼠的FGF21和瘦素血清水平分别降低了26.3%和61.7%（均<0.05）。IT大鼠肾周WAT（pWAT）中成纤维细胞生长因子受体1（FGFR1）及其共受体β-klotho（KLB）的mRNA水平分别是假IT大鼠的1.4倍和2.4倍，FGFR1蛋白水平是假IT大鼠的1.7倍（均<0.05）。与pWAT情况一致，IT大鼠附睾WAT（eWAT）中FGFR1和KLB的蛋白水平显著增加至假IT大鼠的3.0倍和3.9倍（<0.05）。此外，IT大鼠eWAT和pWAT中解偶联蛋白1（UCP1）的蛋白水平也增加至假IT大鼠的2.2倍和2.3倍（<0.05）。然而，与假IT大鼠相比，IT大鼠皮下WAT（sWAT）中FGFR1和KLB的蛋白水平分别降低了34.4%和72.1%（<0.05）。此外，IT大鼠肝脏中FGF21和KLB的蛋白水平分别是假IT大鼠的3.9倍和2.3倍（均<0.05）。IT手术显著降低了糖尿病GK大鼠的脂肪量并改善了葡萄糖代谢。IT手术的这些有益作用可能与其对eWAT和pWAT中FGFR1和KLB表达的刺激作用有关，从而促进这些组织中UCP1的表达。
