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, Saraswathi Viswanathan

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 1 2012

Fingerprint

Fish Oils
Dyslipidemias
Indomethacin
Liver
Lipid Metabolism
Anti-Inflammatory Agents
Cyclooxygenase Inhibitors
Cholesterol Esters
Inflammation
Cytochrome P-450 Enzyme System
Triglycerides
Genes
Lipids
Gene Expression
High Fat Diet
Nutrition
Drinking Water
Protein Isoforms
Fats
Cholesterol

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR-/- mice. / Murali, Ganesan; Milne, Ginger L.; Webb, Corey D.; Stewart, Ann B.; McMillan, Ryan P.; Lyle, Brandon C.; Hulver, Matthew W.; Viswanathan, Saraswathi.

In: Journal of Lipid Research, Vol. 53, No. 10, 01.10.2012, p. 2186-2197.

Research output: Contribution to journalArticle

Murali, G, Milne, GL, Webb, CD, Stewart, AB, McMillan, RP, Lyle, BC, Hulver, MW & Viswanathan, S 2012, 'Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR-/- mice', Journal of Lipid Research, vol. 53, no. 10, pp. 2186-2197. https://doi.org/10.1194/jlr.M029843
Murali, Ganesan ; Milne, Ginger L. ; Webb, Corey D. ; Stewart, Ann B. ; McMillan, Ryan P. ; Lyle, Brandon C. ; Hulver, Matthew W. ; Viswanathan, Saraswathi. / Fish oil and indomethacin in combination potently reduce dyslipidemia and hepatic steatosis in LDLR-/- mice. In: Journal of Lipid Research. 2012 ; Vol. 53, No. 10. pp. 2186-2197.
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