title: Palmitate protects hepatocytes from oxidative stress and triacylglyceride accumulation by stimulation of nitric oxide synthesis in the presence of high glucose and insulin concentration.
abstract: Excessive flux of free fatty acids (FFA) into the liver contributes to liver impairment in non-alcoholic fatty liver disease (NAFLD). It remains unclear how FFA contribute to impairment of hepatocytes. This study treated hepatocytes with linoleic acid and palmitate to investigate the early event triggering FFA-mediated impairment. It determined cell viability, content of nitrite/nitrate and triacylglycerides (TG), inducible nitric oxide synthase (iNOS) protein, oxidation of cardiolipin (CL) as well as formation of F(2)-isoprostanes in the presence of insulin and glucose. Linoleic acid caused significant decrease in cell viability. It is shown that palmitate caused induction of iNOS resulting in increased nitrite/nitrate concentration and slight increase in TG content. Linoleic acid led to a decrease in nitrite/nitrate concentration parallelled by massive TG accumulation in combination with increased oxidation of CL and increased F(2)-isoprostane levels. It is concluded that nitric oxide (NO) concentration regulates FFA-dependent TG accumulation and oxidative stress in rat hepatocytes.
authors.affiliation: Institute of Clinical Chemistry and Pathobiochemistry, Otto-von-Guericke-University Magdeburg, Magdeburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Müller
authors.forename: Andreas
authors.initials: A
authors.lastname: Gardemann
authors.forename: Gerburg
authors.initials: G
authors.lastname: Keilhoff
authors.forename: Daniela
authors.initials: D
authors.lastname: Peter
authors.forename: Ingrid
authors.initials: I
authors.lastname: Wiswedel
authors.forename: Siegfried
authors.initials: S
authors.lastname: Kropf
authors.forename: Lorenz
authors.initials: L
authors.lastname: Schild
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002308:Cardiolipins / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D028441:F2-Isoprostanes / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D022781:Hepatocytes / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008041:Linoleic Acids / Q000494:pharmacology; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D018384:Oxidative Stress; D010168:Palmitates / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D002308:Cardiolipins; D028441:F2-Isoprostanes; D007328:Insulin; D008041:Linoleic Acids; D010168:Palmitates; D014280:Triglycerides; D016718:Arachidonic Acid; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D005947:Glucose