Temporal metabolomic responses of cultured HepG2 liver cells to high fructose and high glucose exposures

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• 作者：John K. Meissen ; Kristin M. Hirahatake ; Sean H. Adams ; Oliver Fiehn
• 关键词：High fructose corn syrup ; Metabolic networks ; Time ; of ; flight mass spectrometry ; Chromatography ; Lipidomics
• 刊名：Metabolomics
• 出版年：2015
• 出版时间：June 2015
• 年：2015
• 卷：11
• 期：3
• 页码：707-721
• 全文大小：3,059 KB
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  Kanehisa, M., Goto, S., Furum
• 作者单位：John K. Meissen (1)
  Kristin M. Hirahatake (3) (4)
  Sean H. Adams (3) (4)
  Oliver Fiehn (1) (2)
  
  1. UC Davis West Coast Metabolomics Center, University of California Davis, 451 Health Sciences Dr., Davis, CA, 95616, USA
  3. Department of Nutrition, University of California Davis, One Shields Avenue., Davis, CA, 95616, USA
  4. Obesity and Metabolism Research Unit, USDA-Agricultural Research Service Western Human Nutrition Research Center, 430 W. Health Sciences Dr., Davis, CA, 95616, USA
  2. Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, PO Box 80203, Jeddah, 21589, Saudi-Arabia
  
• 刊物主题：Biochemistry, general; Molecular Medicine; Cell Biology; Developmental Biology; Biomedicine general;
• 出版者：Springer US
• ISSN：1573-3890

文摘

High fructose consumption has been implicated with deleterious effects on human health, including hyperlipidemia elicited through de novo lipogenesis. 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.