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目的:肥胖是2型糖尿病的高危因素,但脂代谢异常引起胰岛素抵抗的分子机制仍需探讨。去乙酰化酶SIRT1在细胞内的糖脂代谢过程中起着重要的作用,本文应用体内外模型探讨不同类型高脂状态下肝细胞内SIRT1蛋白表达的改变,进而揭示肥胖引起2型糖尿病发病的可能分子途径。方法:分别采用含有不同浓度棕榈酸或油酸的培养液培养HepG2肝细胞1天,检测细胞内SIRT1的蛋白水平;同时采用高脂饲料造小鼠肥胖模型,检测肝脏组织内SIRT1的表达改变。结果:三种不同浓度的棕榈酸均未引起HepG2肝细胞内SIRT1表达的改变,与棕榈酸有所不同,两种浓度的油酸均引起细胞内SIRT1表达的显著降低,分别是对照组的65%和58%。在高脂动物模型中同样未发现肝组织内SIRT1蛋白表达的改变。结论:SIRT1作为细胞内糖脂代谢通路的交叉点,其表达的改变有利于揭示脂代谢异常是如何引起糖代谢紊乱的。油酸的大量摄入可以导致甘油三酯在肝脏中的蓄积和影响肝细胞的胰岛素敏感性,而本文提示油酸诱导的细胞代谢改变很可能通过下调SIRT1来实现,其表达的改变为探讨肥胖引起2型糖尿病的分子机制提供线索。
OBJECTIVE: Obesity is a risk factor for type 2 diabetes. However, the molecular mechanism of insulin resistance caused by abnormal lipid metabolism remains to be explored. Sirtuin SIRT1 plays an important role in intracellular glucose and lipid metabolism. In this study, we used in vitro and in vivo models to explore the changes of SIRT1 protein expression in hepatocytes under different types of hyperlipidemia, and then revealed the pathogenesis of type 2 diabetes Possible molecular pathways. Methods: HepG2 hepatocytes were cultured in culture medium containing different concentrations of palmitic acid or oleic acid for 1 day respectively to detect the protein level of SIRT1 in the cells. At the same time, the mice model of obesity was induced by high fat diet to detect the change of SIRT1 expression in liver tissue. Results: Three different concentrations of palmitic acid did not induce the change of SIRT1 expression in HepG2 hepatocytes. Compared with palmitic acid, both concentrations of oleic acid caused a significant decrease of SIRT1 expression in HepG2 hepatocytes, which was significantly lower than that of control group % And 58%. No change in SIRT1 protein expression in liver tissue was found in the hyperlipidemic animal model. CONCLUSIONS: SIRT1, as the crossover point of intracellular glucose and lipid metabolism, is helpful to reveal how dyslipidemia caused by glucose metabolism disorder. The large intake of oleic acid can lead to the accumulation of triglycerides in the liver and affect the insulin sensitivity of liver cells, and the paper suggests that oleic acid-induced cellular metabolism may be achieved by down-regulation of SIRT1, and its expression changes to explore the obesity Clues to the molecular mechanisms that cause type 2 diabetes.