Ingestion of frying fat leads to activation of the endoplasmic reticulum stress-induced unfolded protein response in the duodenal mucosa of pigs

Ingestion of oxidized fats (OF) causes activation of stress signaling pathways such as nuclear factor-erythroid 2-related factor 2 (Nrf2) in the intestine. Activation of this pathway is mediated by ER stress-induced unfolded protein response (UPR). Herein, we hypothesized that ingestion of OF causes ER stress-induced UPR in duodenal mucosa of pigs.Six-wk-old cross-bred pigs received either a control diet with fresh fat or a diet with OF for 29 days. Pigs fed OF exhibited increased phosphorylation of the ER stress downstream target eukaryotic translation initiation factor 2α and induction of several genes involved in ER stress-induced UPR and Nrf2 target genes in duodenal mucosa. No signs of an impaired intestinal barrier function or a systemic inflammatory response could be found in pigs fed OF.Activation of ER stress-induced UPR by OF in the duodenal mucosa in pigs might be interpreted as a cytoprotective response to stress factors associated with ingestion of OF. Given the similarities between pigs and humans with respect to digestive physiology, it is possible that regular ingestion of fried foods containing OF activates the ER stress-induced UPR also in the intestinal mucosa of humans.