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

Emily G. Armitage; Alan Barnes; Kieran Patrick; Janak Bechar; Matthew J. Harrison; Gareth G. Lavery; G. Ed Rainger; Christopher D. Buckley; Neil J. Loftus; Ian D. Wilson; Amy J. Naylor

doi:10.1007/s11306-020-01764-1

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

Emily G. Armitage, Alan Barnes, Kieran Patrick, Janak Bechar, Matthew J. Harrison, Gareth G. Lavery, G. Ed Rainger, Christopher D. Buckley, Neil J. Loftus, Ian D. Wilson, Amy J. Naylor

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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.

Original language	English
Article number	14
Journal	Metabolomics
Volume	17
Issue number	2
Early online date	18 Jan 2021
DOIs	https://doi.org/10.1007/s11306-020-01764-1
Publication status	Published - 18 Jan 2021

Bibliographical 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.

Keywords

CD248
Endosialin
HRAM UHPLC–MS/MS
High fat diet

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Biochemistry
Clinical Biochemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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http://link.springer.com/10.1007/s11306-020-01764-1

1 Active
2 Finished

Type 14 C-type lectins link endothelial cells and bone remodelling in inflammatory arthiritis
Naylor, A.
ARTHRITIS RESEARCH UK
1/01/18 → 31/12/24
Project: Research
Do Platelets Exacerbate the Atherogenic Process by Regulating the Recruitment, Differentiation and Inflammatory Function of Monocytes
Rainger, E., Nash, G. & Watson, S.
British Heart Foundation
1/09/12 → 31/08/17
Project: Research
Targetting stromal cell subsets in the pathogenesis of imflammatory Arthritis
Buckley, C.
ARTHRITIS RESEARCH CAMPAIGN
1/05/12 → 31/10/18
Project: Research

Cite this

Armitage, E. G., Barnes, A., Patrick, K., Bechar, J., Harrison, M. J., Lavery, G. G., Rainger, G. E., Buckley, C. D., Loftus, N. J., Wilson, I. D., & Naylor, A. 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), Article 14. https://doi.org/10.1007/s11306-020-01764-1

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

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. ",

keywords = "CD248, Endosialin, HRAM UHPLC–MS/MS, High fat diet",

author = "Armitage, {Emily G.} and Alan Barnes and Kieran Patrick and Janak Bechar and Harrison, {Matthew J.} and Lavery, {Gareth G.} and Rainger, {G. Ed} and Buckley, {Christopher D.} and Loftus, {Neil J.} and Wilson, {Ian D.} and Naylor, {Amy J.}",

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.",

year = "2021",

month = jan,

day = "18",

doi = "10.1007/s11306-020-01764-1",

language = "English",

volume = "17",

journal = "Metabolomics",

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TY - JOUR

T1 - Metabolic consequences for mice lacking endosialin

T2 - LC-MS/MS-based metabolic phenotyping of serum from C56Bl/6J control and CD248 knock-out mice

AU - Armitage, Emily G.

AU - Barnes, Alan

AU - Patrick, Kieran

AU - Bechar, Janak

AU - Harrison, Matthew J.

AU - Lavery, Gareth G.

AU - Rainger, G. Ed

AU - Buckley, Christopher D.

AU - Loftus, Neil J.

AU - Wilson, Ian D.

AU - Naylor, Amy J.

N1 - 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.

PY - 2021/1/18

Y1 - 2021/1/18

N2 - 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.

AB - 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.

KW - CD248

KW - Endosialin

KW - HRAM UHPLC–MS/MS

KW - High fat diet

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DO - 10.1007/s11306-020-01764-1

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SN - 1573-3882

VL - 17

JO - Metabolomics

JF - Metabolomics

IS - 2

M1 - 14

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Fingerprint

Projects

Type 14 C-type lectins link endothelial cells and bone remodelling in inflammatory arthiritis

Do Platelets Exacerbate the Atherogenic Process by Regulating the Recruitment, Differentiation and Inflammatory Function of Monocytes

Targetting stromal cell subsets in the pathogenesis of imflammatory Arthritis

Cite this