Palmitate protects hepatocytes from oxidative stress and triacylglyceride accumulation by stimulation of nitric oxide synthesis in the presence of high glucose and insulin concentration

• Published in: Free radical research Vol. 44; no. 12; pp. 1425 - 1434
• Main Authors: Müller, Christian, Gardemann, Andreas, Keilhoff, Gerburg, Peter, Daniela, Wiswedel, Ingrid, Kropf, Siegfried, Schild, Lorenz
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01.12.2010; Taylor & Francis
• Subjects: Adult hepatocyte culture; Animals; Arachidonic Acid - metabolism; Cardiolipins - metabolism; Cell Survival - drug effects; Cells, Cultured; F2-Isoprostanes - metabolism; Glucose - pharmacology; Hepatocytes - drug effects; Hepatocytes - metabolism; Insulin - pharmacology; isoprostanes; linoleic acid; Linoleic Acids - pharmacology; lipid accumulation; Male; Mitochondria - metabolism; nitric oxide; Nitric Oxide - biosynthesis; Nitric Oxide Synthase Type II - biosynthesis; Oxidative Stress; oxidized cardiolipin; palmitate; Palmitates - pharmacology; Rats; Rats, Wistar; Triglycerides - metabolism
• ISSN: 1071-5762; 1029-2470
• DOI: 10.3109/10715762.2010.512919

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 F2-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 F2-isoprostane levels. It is concluded that nitric oxide (NO) concentration regulates FFA-dependent TG accumulation and oxidative stress in rat hepatocytes.