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

Research output: Contribution to journalArticlepeer-review

Authors

  • Emily G. Armitage
  • Alan Barnes
  • Janak Bechar
  • Neil J. Loftus
  • Ian D. Wilson
  • Amy Naylor

External organisations

  • University of Birmingham

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.

Conclusion
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.

Bibliographic note

Funding Information: This study was funded by a Versus Arthritis Career Development Fellowship #21743 awarded to AJN and an Arthritis Research UK (now Versus Arthritis) Programme Grant #19791 awarded to CDB. JB received a Grant from the Jean Shanks Foundation. MJH was supported by a British Heart Foundation (BHF) programme grant (RG/12/7/29693 to GER) and KP was supported by a Collaborative Project Grant from AstraZeneca.

Details

Original languageEnglish
Article number14
Pages (from-to)14
JournalMetabolomics
Volume17
Issue number2
Early online date18 Jan 2021
Publication statusPublished - 18 Jan 2021

Keywords

  • CD248, Endosialin, HRAM UHPLC–MS/MS, High fat diet