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).

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

Profile

Desmoplakins
Palmitates
palmitates
Hep G2 Cells
insulin
Insulin
Genes
Liver
fatty liver
insulin resistance
cytotoxicity
Gene Regulatory Networks
cells
Cytotoxicity
desmosomes
intermediate filaments
genes
Insulin Resistance
keratin
cell adhesion

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

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