Analysis of changes in triacylglycerol ratios in mouse liver and plasma in response to a liver X receptor agonist

Paul Scullion, Darren Edwards, Heather McKinnon, Stewart Miller, David Watson, Lynsey MacIntyre

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

An LC-MS method was developed for the analysis of triacylglycerols (TAG) in mouse liver extracts and plasma samples. C57 Mice were treated with two LXR agonists that have been shown to upregulate TAGs, T0901317 (T1317) or Org 264693 and compared to vehicle dosed animals. The dose used was 30 mg kg(-1), once daily, with three different dose regimes; 24 H, 48 H and 5 day. The TAG ratios measured were C52: 2/C54: 3 and C52: 3/C54: 4, which corresponded to a decrease in the palmitate and an increase in oleate composition of the TAGs. A significant change in the C52: 2/C54: 3 ratio was observed with all dose regimes and a good correlation was obtained between liver and plasma samples. In a separate study, the same compounds were dosed to LXR alpha and LXR beta knock-out (KO) mice at 30 mg kg(-1), once daily, for 5 days. The LXR beta KO mice showed similar TAG ratio changes to the C57 mice, whereas the LXR alpha KO mice showed no change in TAG ratios versus vehicle dosed animals. Measurements of lipid liability in response to an LXR agonist are typically made by measuring total liver TAG levels, which here, only showed a significant effect after the 48 H and 5 day dose regimes. By using a ratio measurement analysis could be performed on plasma samples, greatly simplifying the sample preparation procedure, without the requirement for either calibration curves or an internal standard.

LanguageEnglish
Pages74-85
Number of pages12
JournalMetabolomics
Volume8
Issue number1
DOIs
Publication statusPublished - Feb 2012

Fingerprint

Liver
Triglycerides
Plasmas
Knockout Mice
Animals
Liver Extracts
Palmitates
Oleic Acid
Calibration
Up-Regulation
Liver X Receptors
Lipids
Chemical analysis

Keywords

  • metabolomics
  • triacylglycerol ratios
  • plasma
  • liver X receptor

Cite this

Scullion, Paul ; Edwards, Darren ; McKinnon, Heather ; Miller, Stewart ; Watson, David ; MacIntyre, Lynsey. / Analysis of changes in triacylglycerol ratios in mouse liver and plasma in response to a liver X receptor agonist. In: Metabolomics. 2012 ; Vol. 8, No. 1. pp. 74-85.
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Analysis of changes in triacylglycerol ratios in mouse liver and plasma in response to a liver X receptor agonist. / Scullion, Paul; Edwards, Darren; McKinnon, Heather; Miller, Stewart; Watson, David; MacIntyre, Lynsey.

In: Metabolomics, Vol. 8, No. 1, 02.2012, p. 74-85.

Research output: Contribution to journalArticle

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