Journal
JOURNAL OF LIPID RESEARCH
Volume 53, Issue 10, Pages 2186-2197Publisher
ELSEVIER
DOI: 10.1194/jlr.M029843
Keywords
n-3 fatty acids; cytochrome P450; cholesterol; triglycerides
Categories
Funding
- American Heart Association [0930335N]
- Digestive Disease Research Center at Vanderbilt University [DK 058404]
- National Institutes of Health [GM15431, ES13125, DK-078765]
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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.-Murali, G., G. L. Milne, C. D. Webb, A. B. Stewart, R. P. McMillan, B. C. Lyle, M. W. Hulver, and V. Saraswathi. Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR-/- mice. J. Lipid Res. 2012. 53: 2186-2197.
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