Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR⁻/⁻ mice

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dc.contributor.authorMurali, Ganesanen
dc.contributor.authorMilne, Ginger L.en
dc.contributor.authorWebb, Corey D.en
dc.contributor.authorStewart, Ann B.en
dc.contributor.authorMcMillan, Ryan P.en
dc.contributor.authorLyle, Brandon C.en
dc.contributor.authorHulver, Matthew W.en
dc.contributor.authorSaraswathi, Viswanathanen
dc.contributor.departmentHuman Nutrition, Foods, and Exerciseen
dc.date.accessioned2017-10-12T15:12:51Zen
dc.date.available2017-10-12T15:12:51Zen
dc.date.issued2012-07-29en
dc.description.abstractFish 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-infl ammatory drugs, can enhance the antiinfl ammatory 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. Moreover, 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.en
dc.description.sponsorshipThis project was partly supported by the American Heart Association Scientist Development grant (0930335N) and a Pilot and Feasibility grant from the Digestive Disease Research Center at Vanderbilt University (DK 058404) (V.S.) and by National Institutes of Health grants GM15431 and ES13125 (G.L.M.) and DK-078765 (M.W.H.). Its contents are solely the responsibility of the authors and do not necessarily represent the offi cial views of the National Institutes of Health or other granting agencies.en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1194/jlr.M029843en
dc.identifier.urihttp://hdl.handle.net/10919/79623en
dc.identifier.volume53en
dc.language.isoenen
dc.publisherASBMBen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectn-3 fatty acidsen
dc.subjectcytochrome P450en
dc.subjectcholesterolen
dc.subjecttriglyceridesen
dc.titleFish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR⁻/⁻ miceen
dc.title.serialJournal of Lipid Researchen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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Scholarly Works, Human Nutrition, Foods, and Exercise