A hierarchical approach employing metabolic and gene expression profiles to identify the pathways that confer cytotoxicity in HepG2 cells |
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| Authors: | Zheng Li Shireesh Srivastava Xuerui Yang Sheenu Mittal Paul Norton James Resau Brian Haab Christina Chan |
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| Institution: | (1) Department of Chemical Engineering and Material Science, Michigan State University, East Lansing, MI 48824, USA;(2) Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI 48824, USA;(3) Department of Computer Science and Engineering, Michigan State University, East Lansing, MI 48824, USA;(4) Van Andel Institute, Grand Rapids, MI 49503, USA;(5) Department of Biochemistry and Molecular Biology, Michigan State University, USA |
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| Abstract: | Background Free fatty acids (FFA) and tumor necrosis factor alpha (TNF-α) have been implicated in the pathogenesis of many obesity-related
metabolic disorders. When human hepatoblastoma cells (HepG2) were exposed to different types of FFA and TNF-α, saturated fatty
acid was found to be cytotoxic and its toxicity was exacerbated by TNF-α. In order to identify the processes associated with
the toxicity of saturated FFA and TNF-α, the metabolic and gene expression profiles were measured to characterize the cellular
states. A computational model was developed to integrate these disparate data to reveal the underlying pathways and mechanisms
involved in saturated fatty acid toxicity. |
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