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

Ganesan Murali, Ginger L. Milne, Corey D. Webb, Ann B. Stewart, Ryan P. McMillan, Brandon C. Lyle, Matthew W. Hulver, Viswanathan Saraswathi

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2186-2197
Number of pages12
JournalJournal of Lipid Research
Volume53
Issue number10
DOIs
StatePublished - Oct 2012

Keywords

  • Cholesterol
  • Cytochrome P450
  • Triglycerides
  • n-3 fatty acids

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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    Murali, G., Milne, G. L., Webb, C. D., Stewart, A. B., McMillan, R. P., Lyle, B. C., Hulver, M. W., & Saraswathi, V. (2012). Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR-/- mice. Journal of Lipid Research, 53(10), 2186-2197. https://doi.org/10.1194/jlr.M029843