Lipids up-regulate uncoupling protein 2 expression in rat hepatocytes.

摘要: Abstract Background & Aims: Hepatic steatosis reflects the accumulation of triglycerides and free fatty acids in hepatocytes. Although lipids their metabolites are potentially hepatotoxic, absence overt injury livers suggests that adaptive responses to lipid occur. Fatty induce mitochondrial uncoupling proteins (UCP) 2 3 muscle fat, providing a mechanism dispose excessive acids. hepatocytes do not normally express proteins, UCP-2 is expressed genetically obese mice with livers, suggesting also Methods: To test whether up-regulate hepatocyte UCP-2, cultures rat were treated emulsions, linoleic or oleic acid, expression was evaluated by Northern blotting immunocytochemistry. Because increased reactive oxygen species (ROS) production may contribute lipid-related induction, DNA-binding activity ROS-activated transcription factor, NF-κB, measured, effects tert -butyl hydroperoxide (TBHP) glutathione (GSH) on induction assessed. Results: Lipid emulsions NF-κB resulted dose- time-dependent transcripts cultured hepatocytes; after 24 hours, messenger RNA levels 4.5-fold, protein shown Consistent possibility ROS generated intracellularly during metabolism participates addition cell-impermeable antioxidant GSH did alter UCP-2. Furthermore, TBHP, which known increase production, levels. Conclusions: Lipids Thus, liver adapt an supply substrates inducing facilitate substrate disposal while constraining production. GASTROENTEROLOGY 1999;116:1184-1193