title: Temporal metabolomic responses of cultured HepG2 liver cells to high fructose and high glucose exposures.
abstract: High fructose consumption has been implicated with deleterious effects on human health, including hyperlipidemia elicited throughde novolipogenesis. However, more global effects of fructose on cellular metabolism have not been elucidated. In order to explore the metabolic impact of fructose-containing nutrients, we applied both GC-TOF and HILIC-QTOF mass spectrometry metabolomic strategies using extracts from cultured HepG2 cells exposed to fructose, glucose, or fructose + glucose. Cellular responses were analyzed in a time-dependent manner, incubated in media containing 5.5 mM glucose + 5.0 mM fructose in comparison to controls incubated in media containing either 5.5 mM glucose or 10.5 mM glucose. Mass spectrometry identified 156 unique known metabolites and a large number of unknown compounds, which revealed metabolite changes due to both utilization of fructose and high-carbohydrate loads independent of hexose structure. Fructose was shown to be partially converted to sorbitol, and generated higher levels of fructose-1-phosphate as a precursor for glycolytic intermediates. Differentially regulated ratios of 3-phosphoglycerate to serine pathway intermediates in high fructose media indicated a diversion of carbon backbones away from energy metabolism. Additionally, high fructose conditions changed levels of complex lipids toward phosphatidylethanolamines. Patterns of acylcarnitines in response to high hexose exposure (10.5 mM glucose or glucose/fructose combination) suggested a reduction in mitochondrial beta-oxidation.
authors.affiliation: UC Davis Genome Center, University of California Davis, 451 Health Sciences Dr., Davis, CA 95616, USA ; West Coast Metabolomics Center, University of California Davis, 451 Health Sciences Dr., Davis, CA 95616, USA.
authors.forename: John K
authors.initials: JK
authors.lastname: Meissen
authors.affiliation: Department of Nutrition, University of California Davis, One Shields Avenue., Davis, CA 95616, USA ; Obesity and Metabolism Research Unit, USDA-Agricultural Research Service Western Human Nutrition Research Center, 430 W. Health Sciences Dr., Davis, CA 95616, USA.
authors.forename: Kristin M
authors.initials: KM
authors.lastname: Hirahatake
authors.affiliation: Department of Nutrition, University of California Davis, One Shields Avenue., Davis, CA 95616, USA ; Obesity and Metabolism Research Unit, USDA-Agricultural Research Service Western Human Nutrition Research Center, 430 W. Health Sciences Dr., Davis, CA 95616, USA.
authors.forename: Sean H
authors.initials: SH
authors.lastname: Adams
authors.affiliation: UC Davis Genome Center, University of California Davis, 451 Health Sciences Dr., Davis, CA 95616, USA ; West Coast Metabolomics Center, University of California Davis, 451 Health Sciences Dr., Davis, CA 95616, USA.
authors.forename: Oliver
authors.initials: O
authors.lastname: Fiehn
keywords: chromatography; high fructose corn syrup; lipidomics; metabolic networks; time-of-flight mass spectrometry