Ai Z-L, Zhu C-H, Min M, Wang J, Lan C-H, Fan L-L, Sun W-J, Chen D-F
Department of Gastroenterology and Hepatology, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing, China.
J Int Med Res. 2011;39(4):1219-29. doi: 10.1177/147323001103900410.
Liver X receptor α (LXRα) and sterol regulatory element binding protein-1c (SREBP-1c) were studied in rats with non-alcoholic steatohepatitis (NASH) induced by a high-fat diet. Forty 5-week-old rats were fed either a high-fat diet (n = 30) or a normal diet (n = 10) for 9, 13 or 17 weeks. The mRNA and protein levels for LXRα and SREBP-1c were measured at each time point, as was fatty acid synthase (FAS) activity and the serum levels of free fatty acid (FFA) and triglyceride (TG). The mRNA and protein levels for LXRα and SREBP-1c, FAS activity and serum levels of FFA and TG all significantly increased from week 9 in the high-fat diet rats versus controls. In conclusion, a high-fat diet upregulates LXRα which, in turn, upregulates SREBP-1c, increasing the activity of FAS and FFA and accumulation of TG in hepatocytes. Thus, LXRα and SREBP-1c contribute to the development of NASH.
在高脂饮食诱导的非酒精性脂肪性肝炎（NASH）大鼠中，对肝X受体α（LXRα）和固醇调节元件结合蛋白-1c（SREBP-1c）进行了研究。将40只5周龄大鼠分为两组，分别给予高脂饮食（n = 30）或正常饮食（n = 10），持续9、13或17周。在每个时间点测量LXRα和SREBP-1c的mRNA和蛋白水平，以及脂肪酸合酶（FAS）活性、游离脂肪酸（FFA）和甘油三酯（TG）的血清水平。与对照组相比，高脂饮食大鼠从第9周开始，LXRα和SREBP-1c的mRNA和蛋白水平、FAS活性以及FFA和TG的血清水平均显著升高。总之，高脂饮食上调LXRα，进而上调SREBP-1c，增加FAS活性以及FFA和TG在肝细胞中的积累。因此，LXRα和SREBP-1c促进了NASH的发展。
