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Increased plasma apoM levels impair triglyceride turnover in mice

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  1. Apolipoprotein M and its impact on endothelial dysfunction and inflammation in the cardiovascular system

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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.

Original languageEnglish
Article number158969
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1866
Issue number9
ISSN1388-1981
DOIs
Publication statusPublished - Sep 2021

    Research areas

  • Adipose tissue, Apolipoprotein(s), Fibroblast growth factor 21, Lipase(s), Plasma triglyceride metabolism, Sphingosine-1-phosphate

ID: 66789174