On the mechanism of angiopoietin-like protein 8 for control of lipoprotein lipase activity

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

On the mechanism of angiopoietin-like protein 8 for control of lipoprotein lipase activity. / Kovrov, Oleg; Kristensen, Kristian Kølby; Larsson, Erika; Ploug, Michael; Olivecrona, Gunilla.

In: Journal of Lipid Research, Vol. 60, No. 4, 2019, p. 783-793.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Kovrov, O, Kristensen, KK, Larsson, E, Ploug, M & Olivecrona, G 2019, 'On the mechanism of angiopoietin-like protein 8 for control of lipoprotein lipase activity', Journal of Lipid Research, vol. 60, no. 4, pp. 783-793. https://doi.org/10.1194/jlr.M088807

APA

Kovrov, O., Kristensen, K. K., Larsson, E., Ploug, M., & Olivecrona, G. (2019). On the mechanism of angiopoietin-like protein 8 for control of lipoprotein lipase activity. Journal of Lipid Research, 60(4), 783-793. https://doi.org/10.1194/jlr.M088807

Vancouver

Kovrov O, Kristensen KK, Larsson E, Ploug M, Olivecrona G. On the mechanism of angiopoietin-like protein 8 for control of lipoprotein lipase activity. Journal of Lipid Research. 2019;60(4):783-793. https://doi.org/10.1194/jlr.M088807

Author

Kovrov, Oleg ; Kristensen, Kristian Kølby ; Larsson, Erika ; Ploug, Michael ; Olivecrona, Gunilla. / On the mechanism of angiopoietin-like protein 8 for control of lipoprotein lipase activity. In: Journal of Lipid Research. 2019 ; Vol. 60, No. 4. pp. 783-793.

Bibtex

@article{44486d5d01bb422e933ca147fda4acbc,
title = "On the mechanism of angiopoietin-like protein 8 for control of lipoprotein lipase activity",
abstract = "Angiopoietin-like (ANGPTL) 8 is a secreted inhibitor of LPL, a key enzyme in plasma triglyceride metabolism. It was previously reported that ANGPTL8 requires another member of the ANGPTL family, ANGPTL3, to act on LPL. ANGPTL3, much like ANGPTL4, is a physiologically relevant regulator of LPL activity, which causes irreversible inactivation of the enzyme. Here, we show that ANGPTL8 can form complexes with either ANGPTL3 or ANGPTL4 when the proteins are refolded together from their denatured states. In contrast to the augmented inhibitory effect of the ANGPTL3/ANGPTL8 complex on LPL activity, the ANGPTL4/ANGPTL8 complex is less active compared with ANGPTL4 alone. In our experiments, all three members of the ANGPTL family use the same mechanism to inactivate LPL, which involves dissociation of active dimeric LPL to monomers. This inactivation can be counteracted by the presence of glycosylphosphatidylinositol-anchored HDL binding protein 1, the endothelial LPL transport protein previously known to protect LPL from spontaneous and ANGPTL4-catalyzed inactivation. Our data demonstrate that ANGPTL8 may function as an important metabolic switch, by forming complexes with ANGPTL3, or with ANGPTL4, in order to direct the flow of energy from triglycerides in blood according to the needs of the body.",
author = "Oleg Kovrov and Kristensen, {Kristian K{\o}lby} and Erika Larsson and Michael Ploug and Gunilla Olivecrona",
note = "Copyright {\circledC} 2019 Kovrov et al.",
year = "2019",
doi = "10.1194/jlr.M088807",
language = "English",
volume = "60",
pages = "783--793",
journal = "Journal of Lipid Research",
issn = "0022-2275",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "4",

}

RIS

TY - JOUR

T1 - On the mechanism of angiopoietin-like protein 8 for control of lipoprotein lipase activity

AU - Kovrov, Oleg

AU - Kristensen, Kristian Kølby

AU - Larsson, Erika

AU - Ploug, Michael

AU - Olivecrona, Gunilla

N1 - Copyright © 2019 Kovrov et al.

PY - 2019

Y1 - 2019

N2 - Angiopoietin-like (ANGPTL) 8 is a secreted inhibitor of LPL, a key enzyme in plasma triglyceride metabolism. It was previously reported that ANGPTL8 requires another member of the ANGPTL family, ANGPTL3, to act on LPL. ANGPTL3, much like ANGPTL4, is a physiologically relevant regulator of LPL activity, which causes irreversible inactivation of the enzyme. Here, we show that ANGPTL8 can form complexes with either ANGPTL3 or ANGPTL4 when the proteins are refolded together from their denatured states. In contrast to the augmented inhibitory effect of the ANGPTL3/ANGPTL8 complex on LPL activity, the ANGPTL4/ANGPTL8 complex is less active compared with ANGPTL4 alone. In our experiments, all three members of the ANGPTL family use the same mechanism to inactivate LPL, which involves dissociation of active dimeric LPL to monomers. This inactivation can be counteracted by the presence of glycosylphosphatidylinositol-anchored HDL binding protein 1, the endothelial LPL transport protein previously known to protect LPL from spontaneous and ANGPTL4-catalyzed inactivation. Our data demonstrate that ANGPTL8 may function as an important metabolic switch, by forming complexes with ANGPTL3, or with ANGPTL4, in order to direct the flow of energy from triglycerides in blood according to the needs of the body.

AB - Angiopoietin-like (ANGPTL) 8 is a secreted inhibitor of LPL, a key enzyme in plasma triglyceride metabolism. It was previously reported that ANGPTL8 requires another member of the ANGPTL family, ANGPTL3, to act on LPL. ANGPTL3, much like ANGPTL4, is a physiologically relevant regulator of LPL activity, which causes irreversible inactivation of the enzyme. Here, we show that ANGPTL8 can form complexes with either ANGPTL3 or ANGPTL4 when the proteins are refolded together from their denatured states. In contrast to the augmented inhibitory effect of the ANGPTL3/ANGPTL8 complex on LPL activity, the ANGPTL4/ANGPTL8 complex is less active compared with ANGPTL4 alone. In our experiments, all three members of the ANGPTL family use the same mechanism to inactivate LPL, which involves dissociation of active dimeric LPL to monomers. This inactivation can be counteracted by the presence of glycosylphosphatidylinositol-anchored HDL binding protein 1, the endothelial LPL transport protein previously known to protect LPL from spontaneous and ANGPTL4-catalyzed inactivation. Our data demonstrate that ANGPTL8 may function as an important metabolic switch, by forming complexes with ANGPTL3, or with ANGPTL4, in order to direct the flow of energy from triglycerides in blood according to the needs of the body.

U2 - 10.1194/jlr.M088807

DO - 10.1194/jlr.M088807

M3 - Journal article

VL - 60

SP - 783

EP - 793

JO - Journal of Lipid Research

JF - Journal of Lipid Research

SN - 0022-2275

IS - 4

ER -

ID: 216914267