Lipid peroxides (LOOHs) abound in processed food and have been implicated in the pathology of diverse diseases including gut, cardiovascular, and
cancer diseases. Recently,
RNA Sequencing (
RNA-seq) has been widely used to profile gene expression. To characterize gene expression and pathway dysregulation upon exposure to peroxidized
linoleic acid, we incubated intestinal epithelial cells (Caco-2) with 100 µM of 13-hydroperoxyoctadecadienoic
acid (13-HPODE) or
linoleic acid (LA) for 24 h. Total
RNA was extracted for library preparation and Illumina HiSeq sequencing. We identified 3094 differentially expressed genes (DEGs) in 13-HPODE-treated cells and 2862 DEGs in LA-treated cells relative to untreated cells. We show that
13-HPODE enhanced
lipid metabolic pathways, including
steroid hormone biosynthesis,
PPAR signaling, and bile secretion, which alter
lipid uptake and transport.
13-HPODE and LA treatments promoted detoxification mechanisms including cytochrome-P450. Conversely, both treatments suppressed oxidative phosphorylation. We also show that both treatments may promote absorptive cell differentiation and reduce proliferation by suppressing pathways involved in the cell cycle,
DNA synthesis/repair and ribosomes, and enhancing focal adhesion. A qRT-PCR analysis of representative DEGs validated the
RNA-seq analysis. This study provides insights into mechanisms by which
13-HPODE alters cellular processes and its possible involvement in
mitochondrial dysfunction-related disorders and proposes potential therapeutic strategies to treat LOOH-related pathologies.