Dietary omega-3 polyunsaturated fatty acids attenuate hepatic ischemia/reperfusion injury in rats by modulating toll-like receptor recruitment into lipid rafts

• Published in: Clinical nutrition (Edinburgh, Scotland) Vol. 32; no. 5; pp. 855 - 862
• Main Authors: Kim, Kwangsoon, Jung, Namhee, Lee, Kiho, Choi, Jinwoo, Kim, Sanghun, Jun, Jinhyun, Kim, Eunkyung, Kim, Donghee
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.10.2013; Elsevier
• Subjects: alanine transaminase; Animals; Anti-Inflammatory Agents, Non-Steroidal - therapeutic use; Biological and medical sciences; blood serum; cell membranes; dietary supplements; Dietary Supplements - adverse effects; Disease Models, Animal; Down-Regulation; Fatty Acids, Omega-3 - therapeutic use; Fatty Acids, Omega-6 - adverse effects; Feeding. Feeding behavior; fish oils; Fish Oils - therapeutic use; Fundamental and applied biological sciences. Psychology; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Hepatic ischemia/reperfusion injury; histopathology; immunohistochemistry; inflammation; innate immunity; ischemia; liver; Liver - blood supply; Liver - immunology; Liver - metabolism; Liver Diseases - immunology; Liver Diseases - metabolism; Liver Diseases - pathology; Liver Diseases - prevention & control; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Membrane Microdomains - metabolism; Membrane Microdomains - pathology; omega-3 fatty acids; Omega-3 polyunsaturated fatty acids; omega-6 fatty acids; Other diseases. Semiology; Protein Transport; Rats; Rats, Wistar; Reperfusion Injury - immunology; Reperfusion Injury - metabolism; Reperfusion Injury - pathology; Reperfusion Injury - prevention & control; Signal Transduction; soybean oil; Soybean Oil - adverse effects; Toll-like receptor 4; Toll-Like Receptor 4 - antagonists & inhibitors; Toll-Like Receptor 4 - metabolism; transcription factor NF-kappa B; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Warm Ischemia - adverse effects; Western blotting; Hepatic ischemia/reperfusion injury; ischemia and reperfusion; Omega-3 polyunsaturated fatty acids; ω-3 PUFAs; Toll-like receptor 4; high mobility group box 1; HMGB1; I/R; TLR4; Rat; Rodentia; Cardiovascular disease; Hepatic disease; Lipids; Metabolic diseases; Toll like receptor; n-3 fatty acid; Feeding; Vascular disease; Vertebrata; Mammalia; Diet; Animal; Hepatic ischemia reperfusion injury; Unsaturated fatty acid; Digestive diseases
• ISSN: 0261-5614; 1532-1983
• DOI: 10.1016/j.clnu.2012.11.026

Summary Background & aims Hepatic ischemia/reperfusion (I/R) injury may activate innate immunity through the interaction of toll-like receptor 4 (TLR4) with endogenous ligands. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs) exert suppressive effects on innate immunity through various mechanisms. In this study, we investigated the effect of dietary supplementation with ω-3 PUFAs on hepatic I/R in rats. Methods Three groups of Wistar male rats were fed a standard diet with water, and fish oil as ω-3 PUFAs, or soybean oil as ω-6 PUFAs for 7 days. Subsequently, the rats underwent normothermic, 60 min, partial liver ischemia followed by 6 h of reperfusion. The activation of TLR4 signaling was evaluated using membrane lipid raft isolation. After the 6 h of reperfusion, histopathologic alterations, serum ALT levels, TLR4-mediated inflammation were assessed by western blotting and immunohistochemical study. Results The damage of liver from I/R was diminished by dietary fish oil supplementation. Administration of fish oil inhibited TLR4 receptor recruitment into lipid rafts of cell membrane in liver tissues, which is an initial step required for activation of the downstream signaling pathway. Down-regulation of TLR4-mediated signaling reduced NF-κB activation and consequently, improved I/R injury. Conclusions Dietary ω-3 PUFAs supplementation attenuated hepatic I/R injury and could be considered as a nutritional therapeutic aimed at ameliorating I/R injury.