Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR(-/-) mice.

Murali G, Milne GL, Webb CD, Stewart AB, McMillan RP, Lyle BC, Hulver MW, Saraswathi V
J Lipid Res. 2012 53 (10): 2186-97

PMID: 22847176 · PMCID: PMC3435551 · DOI:10.1194/jlr.M029843

Fish oil (FO) is a potent anti-inflammatory and lipid-lowering agent. Because inflammation can modulate lipid metabolism and vice versa, we hypothesized that combining FO with cyclooxygenase inhibitors (COXIBs), well-known anti-inflammatory drugs, can enhance the anti-inflammatory and lipid-lowering effect of FO. LDLR(-/-) mice were fed a high-fat diet supplemented with 6% olive oil or FO for 12 wk in the presence or absence of indomethacin (Indo, 6 mg/l drinking water). FO reduced plasma total cholesterol by 30% but, in combination with Indo, exerted a greater decrease (44%). The reduction of liver cholesterol ester (CE) and triglycerides (TG) by FO (63% and 41%, respectively) was enhanced by Indo (80% in CE and 64% in TG). FO + Indo greatly increased the expression of genes modulating lipid metabolism and reduced the expression of inflammatory genes compared with control. The mRNA and/or protein expression of pregnane X receptor (PXR) and cytochrome P450 isoforms that alter inflammation and/or lipid metabolism are increased to a greater extent in mice that received FO + Indo. Moroever, the nuclear level of PXR is significantly increased in FO + Indo group. Combining FO with COXIBs may exert their beneficial effects on inflammation and lipid metabolism via PXR and cytochrome P450.

MeSH Terms (15)

Animals Anti-Inflammatory Agents Cytochrome P-450 Enzyme System Dyslipidemias Fatty Liver Female Fish Oils Hypolipidemic Agents Indomethacin Liver Mice Pregnane X Receptor Receptors, LDL Receptors, Steroid RNA, Messenger

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