comparative effects of fructose and glucose on lipogenic gene expression and intermediary metabolism in hepg2 liver cells比较果糖和葡萄糖对脂肪生成的基因表达的影响和中间代谢hepg2肝细胞.pdf

Comparative Effects of Fructose and Glucose on Lipogenic Gene Expression and Intermediary Metabolism in HepG2 Liver Cells Kristin M. Hirahatake1., John K. Meissen2,3., Oliver Fiehn2,3, Sean H. Adams1,4* 1 Departments of Nutrition, University of California Davis, Davis, California, United States of America, 2 Molecular and Cellular Biology, University of California Davis, California, United States of America, 3 Genome Center, University of California Davis, Davis, California, United States of America, 4 Obesity and Metabolism Research Unit, USDA-Agricultural Research Service Western Human Nutrition Research Center, Davis, California, United States of America Abstract Consumption of large amounts of fructose or sucrose increases lipogenesis and circulating triglycerides in humans. Although the underlying molecular mechanisms responsible for this effect are not completely understood, it is possible that as reported for rodents, high fructose exposure increases expression of the lipogenic enzymes fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC-1) in human liver. Since activation of the hexosamine biosynthesis pathway (HBP) is associated with increases in the expression of FAS and ACC-1, it raises the possibility that HBP-related metabolites would contribute to any increase in hepatic expression of these enzymes following fructose exposure. Thus, we compared lipogenic gene expression in human-derived HepG2 cells after incubation in culture medium containing glucose alone or glucose plus 5 mM fructose, using the HBP precursor 10 mM glucosamine (GlcN) as a positive control. Cellular metabolite profiling was conducted to analyze differences between glucose and fructose metabolism. Despite evidence for the active uptake and metabolism of fructose by HepG2 cells, expression of FAS or ACC-1 did not increase in th