title: Exocrine pancreas ER stress is differentially induced by different fatty acids.
abstract: Exocrine pancreas acinar cells have a highly developed endoplasmic reticulum (ER), accommodating their high protein production rate. Overload of dietary fat (typical to obesity) is a recognized risk factor in pancreatitis and pancreatic cancer. Dietary fat, especially saturated fat, has been suggested by others and us to induce an acinar lipotoxic effect. The effect of different dietary fatty acids on the ER stress response is unknown. We studied the effect of acute (24h) challenge with different fatty acids (saturated, mono and poly-unsaturated) at different concentrations (between 200 and 500µM, typical to normal and obese states, respectively), testing fat accumulation, ER stress indicators, X-box binding protein 1 (Xbp1) splicing and nuclear translocation, as well as unfolded protein response (UPR) transcripts and protein levels using exocrine pancreas acinar AR42J and primary cells. Acute exposure of AR42J cells to different fatty acids caused increased accumulation of triglycerides, dependent on the type of fat. Different FAs had different effects on ER stress: most notably, saturated palmitic acid significantly affected the UPR response, as demonstrated by altered Xbp1 splicing, elevation in transcript levels of UPR (Xbp, CHOP, Bip) and immune factors (Tnfα, Tgfβ), and enhanced Xbp1 protein levels and Xbp1 time-dependent nuclear translocation. Poly-unsaturated FAs caused milder elevation of ER stress markers, while mono-unsaturated oleic acid attenuated the ER stress response. Thus, various fatty acids differentially affect acinar cell fat accumulation and, apart from oleic acid, induce ER stress. The differential effect of the various fatty acids could have potential nutritional and therapeutic implications.
authors.affiliation: Department of Nutrition, Faculty of Health Science, Ariel University, Israel.
authors.forename: Hila
authors.initials: H
authors.lastname: Danino
authors.affiliation: Department of Nutrition, Faculty of Health Science, Ariel University, Israel.
authors.forename: Karin
authors.initials: K
authors.lastname: Ben-Dror
authors.affiliation: Department of Nutrition, Faculty of Health Science, Ariel University, Israel. Electronic address: ruthb@ariel.ac.il.
authors.forename: Ruth
authors.initials: R
authors.lastname: Birk
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005227:Fatty Acids / Q000737:chemistry* / Q000494:pharmacology*; D046790:Pancreas, Exocrine / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D005227:Fatty Acids
keywords: ER stress; Exocrine pancreas; Fatty acids