Synergy analysis reveals association between insulin signaling and desmoplakin expression in palmitate treated HepG2 cells

Xuewei Wang, Aritro Nath, Xuerui Yang, Amanda Portis, S. Patrick Walton, Christina Chan

    Research output: Contribution to journalArticle

    • 3 Citations

    Abstract

    The regulation of complex cellular activities in palmitate treated HepG2 cells, and the ensuing cytotoxic phenotype, involves cooperative interactions between genes. While previous approaches have largely focused on identifying individual target genes, elucidating interacting genes has thus far remained elusive. We applied the concept of information synergy to reconstruct a "gene-cooperativity" network for palmititate-induced cytotoxicity in liver cells. Our approach integrated gene expression data with metabolic profiles to select a subset of genes for network reconstruction. Subsequent analysis of the network revealed insulin signaling as the most significantly enriched pathway, and desmoplakin (DSP) as its top neighbor. We determined that palmitate significantly reduces DSP expression, and treatment with insulin restores the lost expression of DSP. Insulin resistance is a common pathological feature of fatty liver and related ailments, whereas loss of DSP has been noted in liver carcinoma. Reduced DSP expression can lead to loss of cell-cell adhesion via desmosomes, and disrupt the keratin intermediate filament network. Our findings suggest that DSP expression may be perturbed by palmitate and, along with insulin resistance, may play a role in palmitate induced cytotoxicity, and serve as potential targets for further studies on non-alcoholic fatty liver disease (NAFLD).

    Original languageEnglish (US)
    Article numbere28138
    JournalPLoS One
    Volume6
    Issue number11
    DOIs
    StatePublished - Nov 23 2011

    Profile

    Desmoplakins
    Palmitates
    Hep G2 Cells
    Insulin
    palmitates
    genes
    Cyclic AMP Receptor Protein
    insulin
    cells
    Fibrin
    Genes
    fatty liver
    insulin resistance
    cytotoxicity
    Gene Regulatory Networks
    Insulin Resistance
    Liver
    Methacholine Compounds
    Ethical Review
    desmosomes

    ASJC Scopus subject areas

    • Agricultural and Biological Sciences(all)
    • Biochemistry, Genetics and Molecular Biology(all)
    • Medicine(all)

    Cite this

    Synergy analysis reveals association between insulin signaling and desmoplakin expression in palmitate treated HepG2 cells. / Wang, Xuewei; Nath, Aritro; Yang, Xuerui; Portis, Amanda; Walton, S. Patrick; Chan, Christina.

    In: PLoS One, Vol. 6, No. 11, e28138, 23.11.2011.

    Research output: Contribution to journalArticle

    Wang, Xuewei; Nath, Aritro; Yang, Xuerui; Portis, Amanda; Walton, S. Patrick; Chan, Christina / Synergy analysis reveals association between insulin signaling and desmoplakin expression in palmitate treated HepG2 cells.

    In: PLoS One, Vol. 6, No. 11, e28138, 23.11.2011.

    Research output: Contribution to journalArticle

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    AU - Portis,Amanda

    AU - Walton,S. Patrick

    AU - Chan,Christina

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