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Increased plasma apoM levels impair triglyceride turnover in mice

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@article{a8715a2812fa4f2fafeb19d079b16d94,
title = "Increased plasma apoM levels impair triglyceride turnover in mice",
abstract = "OBJECTIVE: Apolipoprotein M (apoM) is an essential transporter of plasma Sphingosine-1-Phosphate (S1P), typically attached to all lipoprotein classes, but with a majority bound to high density lipoproteins (HDL). ApoM-deficient mice display an increased activity in brown adipose tissue and a concomitant fast turnover of triglycerides. In what manner apoM/S1P affect the triglyceride metabolism is however still unknown and explored in the present study.METHODS: Triglyceride turnover and potentially associated metabolic pathways were studied in the female human apoM transgenic mouse model (apoM-Tg) with increased plasma apoM and S1P levels. The model was compared with wild type (WT) mice.RESULTS: ApoM-Tg mice had a reduced plasma triglyceride turnover rate and a lower free fatty acid uptake in subcutaneous adipocytes compared to WT mice. Screening for potential molecular mechanisms furthermore revealed a reduction in plasma lipase activity in apoM-Tg animals. Overexpression of apoM also reduced the plasma levels of fibroblast growth factor 21 (FGF21).CONCLUSIONS: The study features the significant role of the apoM/S1P axis in maintaining a balanced triglyceride metabolism. Further, it also highlights the risk of inducing dyslipidaemia in patients receiving S1P-analouges and additionlly emphasizes the apoM/S1P axis as a potential therapeutic target in treatment of hypertriglyceridemia.",
keywords = "Adipose tissue, Apolipoprotein(s), Fibroblast growth factor 21, Lipase(s), Plasma triglyceride metabolism, Sphingosine-1-phosphate",
author = "Stefan Hajny and Anna Borup and Sara Els{\o}e and Christina Christoffersen",
note = "Copyright {\textcopyright} 2021 The Author(s). Published by Elsevier B.V. All rights reserved.",
year = "2021",
month = sep,
doi = "10.1016/j.bbalip.2021.158969",
language = "English",
volume = "1866",
journal = "Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids",
issn = "1388-1981",
publisher = "Elsevier BV",
number = "9",

}

RIS

TY - JOUR

T1 - Increased plasma apoM levels impair triglyceride turnover in mice

AU - Hajny, Stefan

AU - Borup, Anna

AU - Elsøe, Sara

AU - Christoffersen, Christina

N1 - Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.

PY - 2021/9

Y1 - 2021/9

N2 - OBJECTIVE: Apolipoprotein M (apoM) is an essential transporter of plasma Sphingosine-1-Phosphate (S1P), typically attached to all lipoprotein classes, but with a majority bound to high density lipoproteins (HDL). ApoM-deficient mice display an increased activity in brown adipose tissue and a concomitant fast turnover of triglycerides. In what manner apoM/S1P affect the triglyceride metabolism is however still unknown and explored in the present study.METHODS: Triglyceride turnover and potentially associated metabolic pathways were studied in the female human apoM transgenic mouse model (apoM-Tg) with increased plasma apoM and S1P levels. The model was compared with wild type (WT) mice.RESULTS: ApoM-Tg mice had a reduced plasma triglyceride turnover rate and a lower free fatty acid uptake in subcutaneous adipocytes compared to WT mice. Screening for potential molecular mechanisms furthermore revealed a reduction in plasma lipase activity in apoM-Tg animals. Overexpression of apoM also reduced the plasma levels of fibroblast growth factor 21 (FGF21).CONCLUSIONS: The study features the significant role of the apoM/S1P axis in maintaining a balanced triglyceride metabolism. Further, it also highlights the risk of inducing dyslipidaemia in patients receiving S1P-analouges and additionlly emphasizes the apoM/S1P axis as a potential therapeutic target in treatment of hypertriglyceridemia.

AB - OBJECTIVE: Apolipoprotein M (apoM) is an essential transporter of plasma Sphingosine-1-Phosphate (S1P), typically attached to all lipoprotein classes, but with a majority bound to high density lipoproteins (HDL). ApoM-deficient mice display an increased activity in brown adipose tissue and a concomitant fast turnover of triglycerides. In what manner apoM/S1P affect the triglyceride metabolism is however still unknown and explored in the present study.METHODS: Triglyceride turnover and potentially associated metabolic pathways were studied in the female human apoM transgenic mouse model (apoM-Tg) with increased plasma apoM and S1P levels. The model was compared with wild type (WT) mice.RESULTS: ApoM-Tg mice had a reduced plasma triglyceride turnover rate and a lower free fatty acid uptake in subcutaneous adipocytes compared to WT mice. Screening for potential molecular mechanisms furthermore revealed a reduction in plasma lipase activity in apoM-Tg animals. Overexpression of apoM also reduced the plasma levels of fibroblast growth factor 21 (FGF21).CONCLUSIONS: The study features the significant role of the apoM/S1P axis in maintaining a balanced triglyceride metabolism. Further, it also highlights the risk of inducing dyslipidaemia in patients receiving S1P-analouges and additionlly emphasizes the apoM/S1P axis as a potential therapeutic target in treatment of hypertriglyceridemia.

KW - Adipose tissue

KW - Apolipoprotein(s)

KW - Fibroblast growth factor 21

KW - Lipase(s)

KW - Plasma triglyceride metabolism

KW - Sphingosine-1-phosphate

UR - http://www.scopus.com/inward/record.url?scp=85108057523&partnerID=8YFLogxK

U2 - 10.1016/j.bbalip.2021.158969

DO - 10.1016/j.bbalip.2021.158969

M3 - Journal article

C2 - 34051379

VL - 1866

JO - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

JF - Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

SN - 1388-1981

IS - 9

M1 - 158969

ER -

ID: 66789174