Comparative Effects of Fructose and Glucose on Lipogenic Gene Expression and Intermediary Metabolism in HepG2 Liver Cells
Open Access
- 11 November 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (11), e26583
- https://doi.org/10.1371/journal.pone.0026583
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 these cells compared with those incubated with glucose alone. Levels of UDP-N-acetylglucosamine (UDP-GlcNAc), the end-product of the HBP, did not differ significantly between the glucose and fructose conditions. Exposure to 10 mM GlcN for 10 minutes to 24 hours resulted in 8-fold elevated levels of intracellular UDP-GlcNAc (Pin vivo, it would suggest that high fructose consumption promotes triglyceride synthesis primarily through its action to provide lipid precursor carbon and not by activating lipogenic gene expression.Keywords
This publication has 40 references indexed in Scilit:
- Plasma Metabolomic Profiles Reflective of Glucose Homeostasis in Non-Diabetic and Type 2 Diabetic Obese African-American WomenPLOS ONE, 2010
- Increased fructose consumption is associated with fibrosis severity in patients with nonalcoholic fatty liver diseaseHepatology, 2010
- Endocrine and Metabolic Effects of Consuming Fructose- and Glucose-Sweetened Beverages with Meals in Obese Men and Women: Influence of Insulin Resistance on Plasma Triglyceride ResponsesJournal of Clinical Endocrinology & Metabolism, 2009
- Consuming fructose-sweetened, not glucose-sweetened, beverages increases visceral adiposity and lipids and decreases insulin sensitivity in overweight/obese humansJCI Insight, 2009
- Fructose consumption as a risk factor for non-alcoholic fatty liver diseaseJournal of Hepatology, 2008
- Dietary fructose induces a wide range of genes with distinct shift in carbohydrate and lipid metabolism in fed and fasted rat liverBiochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2008
- Metabolic and Endocrine Profiles in Response to Systemic Infusion of Fructose and Glucose in Rhesus MacaquesEndocrinology, 2008
- Effects of four-week high-fructose diet on gene expression in skeletal muscle of healthy menDiabetes & Metabolism, 2008
- Adipocytes with increased hexosamine flux exhibit insulin resistance, increased glucose uptake, and increased synthesis and storage of lipidAmerican Journal of Physiology-Endocrinology and Metabolism, 2005
- Induction of Lipogenic Enzymes in Primary Cultures of Rat HepatocytesEuropean Journal of Biochemistry, 2005