TY - JOUR

T1 - Increased plasma apoM levels impair triglyceride turnover in mice

AU - Hajny, Stefan

AU - Borup, Anna

AU - Elsoe, Sara

AU - Christoffersen, Christina

PY - 2021

Y1 - 2021

N2 - Objective: Apolipopmtein 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 SIP 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: Apolipopmtein 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 SIP 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 - Sphingosine-1-phosphate

KW - Apolipoprotein(s)

KW - Plasma triglyceride metabolism

KW - Lipase(s)

KW - Fibroblast growth factor 21

KW - APOLIPOPROTEIN-M

KW - SPHINGOSINE 1-PHOSPHATE

KW - HEPATIC LIPASE

KW - LIPOPROTEIN-LIPASE

KW - RICH LIPOPROTEINS

KW - BETA-KLOTHO

KW - GROWTH

KW - SPHINGOSINE-1-PHOSPHATE

KW - CHOLESTEROL

KW - METABOLISM

U2 - 10.1016/j.bbalip.2021.158969

DO - 10.1016/j.bbalip.2021.158969

M3 - Journal article

C2 - 34051379

VL - 1866

JO - B B A - Molecular and Cell Biology of Lipids

JF - B B A - Molecular and Cell Biology of Lipids

SN - 1388-1981

IS - 9

M1 - 158969

ER -