Integrated Metabolomics and Transcriptomics Analyses Reveal Metabolic Mechanisms in Porcine Intestinal Epithelial Cells under Zearalenone Stress

Zearalenone
(ZEA) is a mycotoxin that frequently occurs in agricultural
crops and related products and seriously threatens both animal feed
and human food safety. To identify key metabolites and regulators
involved in ZEA toxicological processes, we performed metabolomic
and transcriptomic analyses of porcine IPEC-J2 intestinal epithelial
cells upon ZEA exposure using liquid chromatography–mass spectrometry
(LC–MS)/MS and RNA-seq techniques. A total of 325 differential
metabolites and 5646 differentially expressed genes were detected.
Integrated analyses of metabolomic and transcriptomic data indicated
that metabolic processes including lipid metabolism, amino acid metabolism,
and carbohydrate metabolism were most affected. Exogenous addition
of the key metabolite l-arginine significantly facilitated
ZEA metabolism and ameliorated ZEA-induced reactive oxygen species
levels and cell apoptosis. Furthermore, l -arginine contributed
to the expression of phase II detoxification genes (SULT2B1, GSTA1,
GSTM3, and GPX4). l-Arginine addition also increased the
protein levels of LC3-II and Beclin 1, and downregulated p62/SQSTM1
levels, indicating its regulatory roles in autophagic flux activation
upon ZEA exposure. This study provided global insights into metabolic
and transcriptional changes as well as key metabolites and regulators
underlying the cellular response to ZEA exposure, and paved the way
for the identification of metabolic and molecular targets for biomonitoring
and controlling contamination by ZEA.