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The Strathprints institutional repository is a digital archive of University of Strathclyde research outputs.

Strathprints serves world leading Open Access research by the University of Strathclyde, including research by the Strathclyde Institute of Pharmacy and Biomedical Sciences (SIPBS), where research centres such as the Industrial Biotechnology Innovation Centre (IBioIC), the Cancer Research UK Formulation Unit, SeaBioTech and the Centre for Biophotonics are based.

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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 and Edwards, Darren and McKinnon, Heather and Miller, Stewart and Watson, David and MacIntyre, Lynsey (2012) Analysis of changes in triacylglycerol ratios in mouse liver and plasma in response to a liver X receptor agonist. Metabolomics, 8 (1). pp. 74-85. ISSN 1573-3882

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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.