title: Antifibrotic Effect of Saturated Fatty Acids via Endoplasmic Reticulum Stress Response in Rat Pancreatic Stellate Cells.
abstract: We investigated the effect of saturated fatty acids on chronic pancreatitis pathogenesis by elucidating the endoplasmic reticulum (ER) stress response in pancreatic stellate cells (PSCs), which are major effector cells in pancreatic fibrosis.
  
  
  
  Wistar Bonn/Kobori rats were fed either control diet or high-fat diet (HFD) for 4 weeks. Meanwhile, cultured rat PSCs were stimulated with thapsigargin, an ER stress inducer, or palmitic acid (PA). Pancreatic fibrosis, expressions of fibrosis-related and ER stress-related proteins and mRNA, cell viability, and apoptosis were examined.
  
  
  
  The HFD reduced fibrosis and α-smooth muscle actin expression (ie, activated PSCs) but upregulated ER stress-related mRNA expression in the pancreas of young HFD-fed Wistar Bonn/Kobori rats. Induction of ER stress response in PSCs with thapsigargin or PA induced apoptosis, activated the protein kinase-like ER kinase (PERK) pathway, inhibited cell viability, and downregulated fibrosis-related protein and mRNA expression. The PERK inhibitor negated PA-induced ER stress response.
  
  
  
  Saturated fatty acids can inhibit but may not promote the fibrogenesis of chronic pancreatitis, at least in the early stage, via an ER stress response (ie, the PERK pathway) in PSCs. Moreover, induction of an apoptotic ER stress response in PSCs might be a novel therapeutic strategy for pancreatic fibrosis.
authors.affiliation: From the *Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; and †Digestive Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD.
authors.forename: Lingaku
authors.initials: L
authors.lastname: Lee
authors.forename: Tetsuhide
authors.initials: T
authors.lastname: Ito
authors.forename: Taichi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Robert T
authors.initials: RT
authors.lastname: Jensen
authors.forename: Hisato
authors.initials: H
authors.lastname: Igarashi
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Takayanagi
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D059305:Diet, High-Fat; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005227:Fatty Acids / Q000008:administration & dosage / Q000494:pharmacology*; D005355:Fibrosis / Q000517:prevention & control; D015870:Gene Expression / Q000187:drug effects; D019308:Palmitic Acid / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058954:Pancreatic Stellate Cells / Q000187:drug effects* / Q000378:metabolism; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D000199:Actins; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D019308:Palmitic Acid; D019284:Thapsigargin