| Tracking cellular metabolomics in lipoapoptosis- and steatosis-developing liver cells. | |
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MedLine Citation:
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PMID: 21327189 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Palmitate (PA) is known to induce reactive oxygen species (ROS) formation and apoptosis in liver cells, whereas concurrent treatment of oleate (OA) with PA predominately induces steatosis without ROS in liver cells. We previously reported that PA treatment induces the decoupling of glycolysis and tricarboxylic acid cycle (TCA cycle) fluxes, but OA co-treatment restored most metabolic fluxes to their control levels. However, the mechanisms by which metabolites are linked to metabolic fluxes and subsequent lipoapoptotic or steatotic phenotypes remain unclear. To determine the link, we used GC-MS-based polar and non-polar metabolic profiling in lipoapoptosis- or steatosis-developing H4IIEC3 hepatoma cells, to examine the metabolome at different time points after treatment with either PA alone (PA cells) or both PA and OA (PA/OA cells). Metabolic profiles revealed various changes in metabolite levels for TCA cycle intermediates, pentose phosphate pathway (PPP) intermediates, and energy storage metabolites between PA and PA/OA cells. For example, adenosine was markedly increased only in PA cells, whereas gluconate was increased in PA/OA cells. To assess the interaction among these metabolites, the metabolite-to-metabolite correlations were calculated and correlation networks were visualized. These correlation networks demonstrate that a dissociation among PPP metabolites was introduced in PA-treated cells, and this dissociation was restored in PA/OA-treated cells. Thus, our data suggest that abnormal PPP fluxes, in addition to increased adenosine levels, might be related to the decoupling of glycolysis and the resulting lipoapoptotic phenotype. |
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Authors:
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Yasushi Noguchi; Jamey D Young; Jose O Aleman; Michael E Hansen; Joanne K Kelleher; Gregory Stephanopoulos |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-2-16 |
Journal Detail:
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Title: Molecular bioSystems Volume: - ISSN: 1742-2051 ISO Abbreviation: - Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2011-2-17 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101251620 Medline TA: Mol Biosyst Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge MA 02139, USA. gregstep@mit.edu. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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