title: Effect of α-linolenic acid on endoplasmic reticulum stress-mediated apoptosis of palmitic acid lipotoxicity in primary rat hepatocytes.
abstract: BACKGROUND
  Hepatic inflammation and degeneration induced by lipid depositions may be the major cause of nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the effects of saturated and unsaturated fatty acids (FA) on apoptosis in primary rat hepatocytes.
  
  
  METHODS
  The primary rat hepatocytes were treated with palmitic acid and/or α-linolenic acid in vitro. The expression of proteins associated with endoplasmic reticulum (ER) stress, apoptosis, caspase-3 levels were detected after the treatment.
  
  
  RESULTS
  The treatment with palmitic acid produced a significant increase in cell death. The unfolded protein response (UPR)-associated genes CHOP, GRP78, and GRP94 were induced to higher expression levels by palmitic acid. Co-treatment with α-linolenic acid reversed the apoptotic effect and levels of all three indicators of ER stress exerted by palmitic acid. Tunicamycin, which induces ER stress produced similar effects to those obtained using palmitic acid; its effects were also reversed by α-linolenic acid.
  
  
  CONCLUSIONS
  α-Linolenic acid may provide a useful strategy to avoid the lipotoxicity of dietary palmitic acid and nutrient overload accompanied with obesity and NAFLD.
authors.affiliation: Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, No 157, West 5th Road, Xi'an, Shaanxi Province 710004, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Yang
authors.forename: Hongyang
authors.initials: H
authors.lastname: Shi
authors.forename: Lei
authors.initials: L
authors.lastname: Dong
authors.forename: Jian
authors.initials: J
authors.lastname: Bai
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000502:physiology; D005234:Fatty Liver / Q000503:physiopathology; D015870:Gene Expression; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects* / Q000502:physiology; D065626:Non-alcoholic Fatty Liver Disease; D019308:Palmitic Acid / Q000633:toxicity*; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D013312:Stress, Physiological / Q000187:drug effects*; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology; D056811:Unfolded Protein Response / Q000187:drug effects; D017962:alpha-Linolenic Acid / Q000494:pharmacology*; D000091342:Endoplasmic Reticulum Chaperone BiP
chemical_list: D006360:Heat-Shock Proteins; D019308:Palmitic Acid; D051742:Transcription Factor CHOP; D014415:Tunicamycin; D017962:alpha-Linolenic Acid; C497251:Ddit3 protein, rat; C051684:GRP78 protein, rat; D000091342:Endoplasmic Reticulum Chaperone BiP