Effect of High-fat Diet on Cholesterol Metabolism in Rats and Its Association with Na＋/K＋-ATPase/Src/pERK Signaling Pathway

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences 2015-08, Vol.35 (4), p.490-494
• Main Authors: Wang, Li, Xu, Fei, Zhang, Xue-jun, Jin, Run-ming, Li, Xin
• Format: Article
• Language: English
• Subjects: Acyl Coenzyme A - genetics; Acyl Coenzyme A - metabolism; Animals; Cell Membrane - metabolism; Cholesterol - blood; Cytoplasm - metabolism; Diet, High-Fat - adverse effects; Gene Expression Regulation - drug effects; HMG-CoA还原酶; Lipid Metabolism - drug effects; Liver - metabolism; Male; MAP Kinase Signaling System - drug effects; Medicine; Medicine & Public Health; Rats; Rats, Sprague-Dawley; Sodium-Potassium-Exchanging ATPase - genetics; Sodium-Potassium-Exchanging ATPase - metabolism; Sterol Regulatory Element Binding Protein 2 - genetics; Sterol Regulatory Element Binding Protein 2 - metabolism; Western印迹; 低密度脂蛋白胆固醇; 信号通路; 胆固醇代谢; 雄性大鼠; 高密度脂蛋白胆固醇; 高脂饮食
• ISSN: 1672-0733; 1993-1352
• DOI: 10.1007/s11596-015-1458-6

Summary： Abnormal cholesterol metabolism is associated with an elevated risk of developing athero- sclerosis, hypertension, and diabetes etc. Na＋/K＋-ATPase was found to regulate cholesterol synthesis, distribution and trafficking. This study aimed to examine the effect of high-fat diet on cholesterol me- tabolism in rats and the role of Na＋/K＋-ATPase/Src/ERK signaling pathway in the process. Forty male SD rats were evenly divided into high-fat diet group and control group at random. Animals in the former group were fed on high-fat diet for 12 weeks, and those fed on basic diet served as control. Blood lipids, including total cholesterol （TC）, triglyceride （TG）, high density lipoprotein-cholesterol （HDL-C）, and low density lipoprotein-cholesteral （LDL-C） levels, were detected at 3, 6 and 12 weeks. The ratio of cholesterol content in cytoplasm to that in cell membrane was detected in liver tissues. RT-PCR and Western blotting were used to measure the expression of lipid metabolism-associated genes （HMG-CoA reductase and SREBP-2） after 12-week high-fat diet. Na＋/K＋-ATPase/Src/ERK signaling path- way-related components （Na＋/K＋-ATPase ctl, Src-PY418 and pERK1/2） were also measured by West- ern blotting. The results showed that the serum TC, TG, and LDL-C levels were significantly higher in high-fat diet group than those in control group, while the HDL-C level was significantly lower in high-fat diet group at 6 weeks （P〈0.01）. High-fat diet led to an increase in the cholesterol content in the cytoplasm and cell membrane. The ratio of cholesterol content in cytoplasm to that in cell membrane was elevated over time. The expression of HMG-CoA reductase and SREBP-2 was significantly sup- pressed at mRNA and protein levels after 12-week high-fat diet （P〈0.05）. Moreover, high-fat diet pro- moted the expression of Na＋/K＋-ATPase α1 but suppressed the phosphorylation of Src-PY418 and ERK1/2 at 12 weeks （P〈0.05）. It was concluded that high-fat diet regulates cholesterol metabolism, and Na＋/K＋-ATPase signaling pathway is involved in the process possibly by regulating the expression of lipid metabolism-associated proteins HMG-CoA reductase and SREBP-2.