瞬时受体电位通道蛋白5在糖脂代谢中的作用研究

Role of transient receptor potential channel protein 5 in glycolipid metabolism

目的研究TRPC5在糖脂代谢过程中的作用。方法选用C57BL/6J与TRPC5-/-♂小鼠各10只,随机分为对照组与高糖组,每周测定小鼠体重与空腹血糖。8周后,用试剂盒测定血清中insulin含量;肝脏组织中CS、ACC、FAS、NEFA和糖原含量;血清及肝脏组织中HK、PFK、PK、PA、TC、TG、LDL-C和HDL-C含量。同时,测定皮下脂肪组织中FAS与NEFA含量。另使用RNA-Sequence技术对肝脏组织进行转录组测序与数据分析。结果对照组TRPC5-/-小鼠血清中insulin、HDL-C及肝脏组织中TG与糖原含量较C57BL/6J组低(P<0.05);血清中TC和TG,以及肝脏组织中NEFA含量较C57BL/6J组高(P<0.05)。高糖组TRPC5-/-小鼠血清中insulin、PFK及肝脏组织中ACC含量高于C57BL/6J组(P<0.05)。RNA-Sequence结果显示高糖刺激后,TRPC5基因影响代谢通路、产热和内分泌抵抗过程。结论TRPC5与糖脂代谢过程有关。高糖刺激下,TRPC5基因能抑制糖酵解,影响脂肪酸合成,进而影响脂肪代谢;同时促进糖原合成,维持糖脂代谢动态平衡。

Aim To investigate the role of the transient receptor potential channel protein 5(TRPC5)in the process of glycolipid conversion.Methods C57BL/6J and TRPC5-/-mice were randomly divided into control group(n=5)and high sucrose group(n=5).Fasting blood glucose(FBG)and the change of body weight were monitored every 7 days.The levels of insulin in serum,citroyl synthetase(CS),acetyl-CoA carboxylase(ACC),fatty acid synthase(FAS),nonesterified fatty acid(NEFA),glycogen in liver tissues,the levels of hexokinase(HK),6-phosphofructokinase(PFK),pyruvate kinase(PK),pyruvic acid,total cholesterol(TC),triglyceride(TG),low density lipoprotein(LDL-C),high density lipoprotein(HDL-C)in serum and liver tissues were measured after administration.FAS and NEFA in subcutaneous fat were measured respectively.And RNA sequence technology was used to sequence the transcriptome of liver tissues.Differentially expressed genes were assessed the relationship between them was explored.Results Compared with C57BL/6J mice,the level of insulin,HDL-C in serum,and TG,glycogen in liver tissues markedly decreased in TRPC5 knock-out mice(P<0.05).While levels of the TG and TC in serum as well as NEFA,in liver tissues increased in control group(P<0.05).The levels of insulin,PFK in serum and ACC in liver tissues of TRPC5 knock-out mice were higher than those of C57BL/6J mice under the stimulation of high sucrose(P<0.05).RNA sequence analysis also showed that TRPC5 gene could affect metabolic pathway,thermogenesis and endocrine resistance under the stimulation of high sucrose.Conclusions Result of this study uncover that TRPC5 gene regulates the process of glycolipid metabolism under the stimulation of high sucrose.TRPC5 gene can promote glycogen synthesis,inhibit glycolysis and affect fatty acid synthesis,and maintain the dynamic balance of glycolipid metabolism as well.