Metabolic consequences for mice lacking Endosialin: LC-MS/MS-based metabolic phenotyping of serum from C56Bl/6J Control and CD248 knock-out mice

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Armitage, Emily G, Barnes, Alan, Patrick, Kieran, Bechar, Janak, Harrison, Matthew J, Lavery, Gareth G, Rainger, G Ed, Buckley, Christopher D, Loftus, Neil J, Wilson, Ian D ORCID: 0000-0002-8558-7394 et al (show 1 more authors) and Naylor, Amy J (2021) Metabolic consequences for mice lacking Endosialin: LC-MS/MS-based metabolic phenotyping of serum from C56Bl/6J Control and CD248 knock-out mice. METABOLOMICS, 17 (2). 14-.

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Official URL: http://dx.doi.org/10.1007/s11306-020-01764-1

Abstract

<h4>Introduction</h4>The Endosialin/CD248/TEM1 protein is expressed in adipose tissue and its expression increases with obesity. Recently, genetic deletion of CD248 has been shown to protect mice against atherosclerosis on a high fat diet.<h4>Objectives</h4>We investigated the effect of high fat diet feeding on visceral fat pads and circulating lipid profiles in CD248 knockout mice compared to controls.<h4>Methods</h4>From 10 weeks old, CD248<sup>-/-</sup> and <sup>+/+</sup> mice were fed either chow (normal) diet or a high fat diet for 13 weeks. After 13 weeks the metabolic profiles and relative quantities of circulating lipid species were assessed using ultra high performance liquid chromatography-quadrupole time-of flight mass spectrometry (UHPLC-MS) with high resolution accurate mass (HRAM) capability.<h4>Results</h4>We demonstrate a specific reduction in the size of the perirenal fat pad in CD248<sup>-/-</sup> mice compared to CD248<sup>+/+</sup>, despite similar food intake. More strikingly, we identify significant, diet-dependent differences in the serum metabolic phenotypes of CD248 null compared to age and sex-matched wildtype control mice. Generalised protection from HFD-induced lipid accumulation was observed in CD248 null mice compared to wildtype, with particular reduction noted in the lysophosphatidylcholines, phosphatidylcholines, cholesterol and carnitine.<h4>Conclusions</h4>Overall these results show a clear and protective metabolic consequence of CD248 deletion in mice, implicating CD248 in lipid metabolism or trafficking and opening new avenues for further investigation using anti-CD248 targeting agents.

Item Type:	Article
Uncontrolled Keywords:	CD248, Endosialin, High fat diet, HRAM UHPLC-MS, MS
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	17 Feb 2023 14:33
Last Modified:	17 Feb 2023 14:33
DOI:	10.1007/s11306-020-01764-1
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3168488