Metabolic consequences for mice lacking Endosialin: LC–MS/MS-based metabolic phenotyping of serum from C56Bl/6J Control and CD248 knock‐out mice
Open Access
- 18 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Metabolomics
- Vol. 17 (2), 1-11
- https://doi.org/10.1007/s11306-020-01764-1
Abstract
Introduction 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. Objectives We investigated the effect of high fat diet feeding on visceral fat pads and circulating lipid profiles in CD248 knockout mice compared to controls. Methods From 10 weeks old, CD248−/− and +/+ 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. Results We demonstrate a specific reduction in the size of the perirenal fat pad in CD248−/− mice compared to CD248+/+, 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. Conclusions 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.Funding Information
- Versus Arthritis (21743)
- Versus Arthritis (19791)
- Jean Shanks Foundation
- AstraZeneca
This publication has 36 references indexed in Scilit:
- Phosphatidylcholine Transfer Protein Interacts with Thioesterase Superfamily Member 2 to Attenuate Insulin SignalingScience Signaling, 2013
- CD248+ stromal cells are associated with progressive chronic kidney diseaseKidney International, 2011
- CD248 facilitates tumor growth via its cytoplasmic domainBMC Cancer, 2011
- Endosialin/TEM-1/CD248 regulates pericyte proliferation through PDGF receptor signalingCancer Biology & Therapy, 2010
- Hypoxia upregulates expression of human endosialin gene via hypoxia-inducible factor 2British Journal of Cancer, 2008
- Within-Day Reproducibility of an HPLC−MS-Based Method for Metabonomic Analysis: Application to Human UrineJournal of Proteome Research, 2007
- Metabolism of phosphatidylcholine and its implications for lipid acyl chain composition in Saccharomyces cerevisiaeBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2007
- A pragmatic and readily implemented quality control strategy for HPLC-MS and GC-MS-based metabonomic analysisThe Analyst, 2006
- Endosialin (TEM1, CD248) is a marker of stromal fibroblasts and is not selectively expressed on tumour endotheliumFEBS Letters, 2005
- Vascular Remodeling Induced by Naturally Occurring Unsaturated Lysophosphatidic Acid In VivoJournal of the American College of Cardiology, 2003