Peroxidized Linoleic Acid, 13-HPODE, Alters Gene Expression Profile in Intestinal Epithelial Cells
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 dysregula...
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doaj-7b9ab6cbba3640c59d781fd742efb9312021-02-04T00:03:32ZengMDPI AGFoods2304-81582021-02-011031431410.3390/foods10020314Peroxidized Linoleic Acid, 13-HPODE, Alters Gene Expression Profile in Intestinal Epithelial CellsNisreen Faizo0Chandrakala Aluganti Narasimhulu1Anna Forsman2Shibu Yooseph3Sampath Parthasarathy4Burnett School of Biomedical Sciences, Genomics and Bioinformatics Cluster, College of Medicine, University of Central Florida, Orlando, FL 32816, USABurnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USADepartment of Biology, Genomics and Bioinformatics Cluster, University of Central Florida, Orlando, FL 32816, USADepartment of Computer Science, Genomics and Bioinformatics Cluster, University of Central Florida, Orlando, FL 32816, USABurnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32816, USALipid 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.https://www.mdpi.com/2304-8158/10/2/314lipid peroxidationgene expressionmetabolism |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nisreen Faizo Chandrakala Aluganti Narasimhulu Anna Forsman Shibu Yooseph Sampath Parthasarathy |
spellingShingle |
Nisreen Faizo Chandrakala Aluganti Narasimhulu Anna Forsman Shibu Yooseph Sampath Parthasarathy Peroxidized Linoleic Acid, 13-HPODE, Alters Gene Expression Profile in Intestinal Epithelial Cells Foods lipid peroxidation gene expression metabolism |
author_facet |
Nisreen Faizo Chandrakala Aluganti Narasimhulu Anna Forsman Shibu Yooseph Sampath Parthasarathy |
author_sort |
Nisreen Faizo |
title |
Peroxidized Linoleic Acid, 13-HPODE, Alters Gene Expression Profile in Intestinal Epithelial Cells |
title_short |
Peroxidized Linoleic Acid, 13-HPODE, Alters Gene Expression Profile in Intestinal Epithelial Cells |
title_full |
Peroxidized Linoleic Acid, 13-HPODE, Alters Gene Expression Profile in Intestinal Epithelial Cells |
title_fullStr |
Peroxidized Linoleic Acid, 13-HPODE, Alters Gene Expression Profile in Intestinal Epithelial Cells |
title_full_unstemmed |
Peroxidized Linoleic Acid, 13-HPODE, Alters Gene Expression Profile in Intestinal Epithelial Cells |
title_sort |
peroxidized linoleic acid, 13-hpode, alters gene expression profile in intestinal epithelial cells |
publisher |
MDPI AG |
series |
Foods |
issn |
2304-8158 |
publishDate |
2021-02-01 |
description |
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. |
topic |
lipid peroxidation gene expression metabolism |
url |
https://www.mdpi.com/2304-8158/10/2/314 |
work_keys_str_mv |
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