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Larsson, Mikael
Publications (10 of 11) Show all publications
Meyers, N. L., Larsson, M., Olivecrona, G. & Small, D. M. (2015). A Pressure-dependent Model for the Regulation of Lipoprotein Lipase by Apolipoprotein C-II. Journal of Biological Chemistry, 290(29), 18029-18044
Open this publication in new window or tab >>A Pressure-dependent Model for the Regulation of Lipoprotein Lipase by Apolipoprotein C-II
2015 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 290, no 29, p. 18029-18044Article in journal (Refereed) Published
Abstract [en]

Apolipoprotein C-II (apoC-II) is the co-factor for lipoprotein lipase (LPL) at the surface of triacylglycerol-rich lipoproteins. LPL hydrolyzes triacylglycerol, which increases local surface pressure as surface area decreases and amphipathic products transiently accumulate at the lipoprotein surface. To understand how apoC-II adapts to these pressure changes, we characterized the behavior of apoC-II at multiple lipid/water interfaces. ApoC-II adsorption to a triacylglycerol/water interface resulted in large increases in surface pressure. ApoC-II was exchangeable at this interface and desorbed on interfacial compressions. These compressions increase surface pressure and mimic the action of LPL. Analysis of gradual compressions showed that apoC-II undergoes a two-step desorption, which indicates that lipid-bound apoC-II can exhibit at least two conformations. We characterized apoC-II at phospholipid/triacylglycerol/water interfaces, which more closely mimic lipoprotein surfaces. ApoC-II had a large exclusion pressure, similar to that of apoC-I and apoC-III. However, apoC-II desorbed at retention pressures higher than those seen with the other apoCs. This suggests that it is unlikely that apoC-I and apoC-III inhibit LPL via displacement of apoC-II from the lipoprotein surface. Upon rapid compressions and re-expansions, re-adsorption of apoC-II increased pressure by lower amounts than its initial adsorption. This indicates that apoC-II removed phospholipid from the interface upon desorption. These results suggest that apoC-II regulates the activity of LPL in a pressure-dependent manner. ApoC-II is provided as a component of triacylglycerol-rich lipoproteins and is the co-factor for LPL as pressure increases. Above its retention pressure, apoC-II desorbs and removes phospholipid. This triggers release of LPL from lipoproteins.

Place, publisher, year, edition, pages
Bethesda: American Society for Biochemistry and Molecular Biology, 2015
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-107297 (URN)10.1074/jbc.M114.629865 (DOI)000358511700035 ()26026161 (PubMedID)
Available from: 2015-08-27 Created: 2015-08-21 Last updated: 2018-06-07Bibliographically approved
Meyers, N., Larsson, M., Olivecrona, G. & Small, D. (2015). A pressure-dependent model for the regulation of lipoprotein lipase by apolipoprotein C-II. The FASEB Journal, 29(Supplement 1), Article ID 886.8.
Open this publication in new window or tab >>A pressure-dependent model for the regulation of lipoprotein lipase by apolipoprotein C-II
2015 (English)In: The FASEB Journal, ISSN 0892-6638, E-ISSN 1530-6860, Vol. 29, no Supplement 1, article id 886.8Article in journal, Meeting abstract (Other academic) Published
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-111022 (URN)000361722705017 ()
Available from: 2015-11-02 Created: 2015-11-02 Last updated: 2018-06-07Bibliographically approved
Reimund, M., Larsson, M., Kovrov, O., Kasvandik, S., Olivecrona, G. & Lookene, A. (2015). Evidence for Two Distinct Binding Sites for Lipoprotein Lipase on Glycosylphosphatidylinositol-anchored High Density Lipoprotein-binding Protein 1 (GPIHBP1). Journal of Biological Chemistry, 290(22), 13919-13934
Open this publication in new window or tab >>Evidence for Two Distinct Binding Sites for Lipoprotein Lipase on Glycosylphosphatidylinositol-anchored High Density Lipoprotein-binding Protein 1 (GPIHBP1)
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2015 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 290, no 22, p. 13919-13934Article in journal (Refereed) Published
Abstract [en]

GPIHBP1 is an endothelial membrane protein that transports lipoprotein lipase (LPL) from the subendothelial space to the luminal side of the capillary endothelium. Here, we provide evidence that two regions of GPIHBP1, the acidic N-terminal domain and the central Ly6 domain, interact with LPL as two distinct binding sites. This conclusion is based on comparative binding studies performed with a peptide corresponding to the N-terminal domain of GPIHBP1, the Ly6 domain of GPIHBP1, wild type GPIHBP1, and the Ly6 domain mutant GPIHBP1 Q114P. Although LPL and the N-terminal domain formed a tight but short lived complex, characterized by fast on-and off-rates, the complex between LPL and the Ly6 domain formed more slowly and persisted for a longer time. Unlike the interaction of LPL with the Ly6 domain, the interaction of LPL with the N-terminal domain was significantly weakened by salt. The Q114P mutant bound LPL similarly to the N-terminal domain of GPIHBP1. Heparin dissociated LPL from the N-terminal domain, and partially from wild type GPIHBP1, but was unable to elute the enzyme from the Ly6 domain. When LPL was in complex with the acidic peptide corresponding to the N-terminal domain of GPIHBP1, the enzyme retained its affinity for the Ly6 domain. Furthermore, LPL that was bound to the N-terminal domain interacted with lipoproteins, whereas LPL bound to the Ly6 domain did not. In summary, our data suggest that the two domains of GPIHBP1 interact independently with LPL and that the functionality of LPL depends on its localization on GPIHBP1.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2015
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-105251 (URN)10.1074/jbc.M114.634626 (DOI)000355313000024 ()25873395 (PubMedID)
Available from: 2015-06-24 Created: 2015-06-22 Last updated: 2018-06-07Bibliographically approved
Caraballo, R., Larsson, M., Nilsson, S. K., Ericsson, M., Qian, W., Tran, N. P., . . . Elofsson, M. (2015). Structure-activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo. European Journal of Medicinal Chemistry, 103, 191-209
Open this publication in new window or tab >>Structure-activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo
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2015 (English)In: European Journal of Medicinal Chemistry, ISSN 0223-5234, E-ISSN 1768-3254, Vol. 103, p. 191-209Article in journal (Refereed) Published
Abstract [en]

The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Common. 2014, 450, 1063). Herein, we establish structure activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo. 2015 The Authors. Published by Elsevier Masson SAS.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Lipoprotein lipase, LPL, Triglyceride, Structure-activity relationship, Agonist
National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-111481 (URN)10.1016/j.ejmech.2015.08.058 (DOI)000363344700015 ()26355531 (PubMedID)
Available from: 2015-12-08 Created: 2015-11-13 Last updated: 2018-06-07Bibliographically approved
Larsson, M. (2014). Endogenous and exogenous factors affecting lipoprotein lipase activity. (Doctoral dissertation). Umeå: Umeå University
Open this publication in new window or tab >>Endogenous and exogenous factors affecting lipoprotein lipase activity
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Individuals with high levels of plasma triglycerides are at high risk to develop cardiovascular disease (CVD), currently one of the major causes of death worldwide. Recent epidemiological studies show that loss-of-function mutations in the APOC3 gene lower plasma triglyceride levels and reduce the incidence of coronary artery disease. The APOC3 gene encodes for apolipoprotein (APO) C3, known as an inhibitor of lipoprotein lipase (LPL) activity. Similarly, a common gain-of-function mutation in the LPL gene is associated with reduced risk for CVD.

LPL is central for the metabolism of lipids in blood. The enzyme acts at the endothelial surface of the capillary bed where it hydrolyzes triglycerides in circulating triglyceride-rich lipoproteins (TRLs) and thereby allows uptake of fatty acids in adjacent tissues. LPL activity has to be rapidly modulated to adapt to the metabolic demands of different tissues. The current view is that LPL is constitutively expressed and that the rapid modulation of the enzymatic activity occurs by some different controller proteins. Angiopoietin-like protein 4 (ANGPTL4) is one of the main candidates for control of LPL activity. ANGPTL4 causes irreversible inactivation through dissociation of the active LPL dimer to inactive monomers. Other proteins that have effects on LPL activity are the APOCs which are surface components of the substrate TRLs. APOC2 is a well-known LPL co-factor, whereas APOC1 and APOC3 independently inhibit LPL activity.

Given the important role of LPL for triglyceride homeostasis in blood, the aim of this thesis was to find small molecules that could increase LPL activity and serve as lead compounds in future drug discovery efforts. Another aim was to investigate the molecular mechanisms for how APOC1 and APOC3 inhibit LPL activity.

Using a small molecule screening library we have identified small molecules that can protect LPL from inactivation by ANGPTL4 during incubations in vitro. Following a structure-activity relationship study we have synthesized lead compounds that more efficiently protect LPL from inactivation by ANGPTL4 in vitro and also have dramatic triglyceride-lowering properties in vivo. In a separate study we show that low concentrations of fatty acids possess the ability to prevent inactivation of LPL by ANGPTL4 under in vitro conditions.

With regard to APOC1 and APOC3 we demonstrate that when bound to TRLs, these apolipoproteins prevent binding of LPL to the lipid/water interface. This results in decreased lipolysis and in an increased susceptibility of LPL to inactivation by ANGPTL4. We demonstrate that hydrophobic amino acid residues that are centrally located in the APOC3 molecule are critical for attachment of this protein to lipid emulsion particles and consequently for inhibition of LPL activity.

In summary, this work has identified a lead compound that protects LPL from inactivation by ANGPTL4 in vitro and lowers triglycerides in vivo. In addition, we propose a molecular mechanism for inhibition of LPL activity by APOC1 and APOC3.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2014. p. 56
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1669
Keywords
LPL, APOC1, APOC2, APOC3, ANGPTL4, enzyme inactivation, lipoprotein metabolism, triglycerides, fatty acids, hypertriglyceridemia, CVD, small molecule screening, structure-activity relationship
National Category
Cell and Molecular Biology
Research subject
Medicine, cardiovascular disease
Identifiers
urn:nbn:se:umu:diva-91662 (URN)978-91-7601-115-7 (ISBN)
Public defence
2014-08-27, NUS - Norrlands universitetssjukhus, Sal E04, Byggnad 6E, Umeå Universitet, Umeå, 14:00 (English)
Opponent
Supervisors
Available from: 2014-08-15 Created: 2014-08-13 Last updated: 2018-06-07Bibliographically approved
Larsson, M., Caraballo, R., Ericsson, M., Lookene, A., Enquist, P.-A., Elofsson, M., . . . Olivecrona, G. (2014). Identification of a small molecule that stabilizes lipoprotein lipase in vitro and lowers triglycerides in vivo. Biochemical and Biophysical Research Communications - BBRC, 450(2), 1063-1069
Open this publication in new window or tab >>Identification of a small molecule that stabilizes lipoprotein lipase in vitro and lowers triglycerides in vivo
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2014 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 450, no 2, p. 1063-1069Article in journal (Refereed) Published
Abstract [en]

Patients at increased cardiovascular risk commonly display high levels of plasma triglycerides (TGs) levels, elevated LDL cholesterol, small dense LDL particles and low levels of HDL-cholesterol. Many remain at high risk even after successful statin therapy, presumably because TG levels remain high. Lipoprotein lipase (LPL) maintains TG homeostasis in blood by hydrolysis of TG-rich lipoproteins. Efficient clearance of TGs is accompanied by increased levels of HDL-cholesterol and decreased levels of small dense LDL. Given the central role of LPL in lipid metabolism we sought to find small molecules that could increase LPL activity and serve as starting points for drug development efforts against cardiovascular disease. Using a small molecule screening approach we have identified small molecules that can protect LPL from inactivation by the controller protein angiopoietin-like protein 4 during incubations in vitro. One of the selected compounds, 50F10, was directly shown to preserve the active homodimer structure of LPL, as demonstrated by heparin-Sepharose chromatography. This compound tended to reduce fasting TG levels in normal rats. On injection to hypertriglyceridemic apolipoprotein A-V deficient mice the compound ameliorated the postprandial response after an olive oil gavage. This compound is a potential lead compound for the development of drugs that could reduce the residual risk associated with elevated TGs in dyslipidemia.

Place, publisher, year, edition, pages
Elsevier, 2014
Keywords
Lipoprotein lipase, Angiopoietin-like protein 4, Hypertriglyceridemia, Lipoprotein metabolism, Cardiovascular disease, Small molecule screening
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-91689 (URN)10.1016/j.bbrc.2014.06.114 (DOI)000339861200023 ()24984153 (PubMedID)
Funder
Swedish Research CouncilVINNOVAKnut and Alice Wallenberg FoundationCarl Tryggers foundation
Available from: 2014-08-13 Created: 2014-08-13 Last updated: 2018-06-07Bibliographically approved
Plengpanich, W., Young, S. G., Khovidhunkit, W., Bensadoun, A., Karnman, H., Ploug, M., . . . Beigneux, A. P. (2014). Multimerization of clycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) and familial chylomicronemia from a serine-to-cysteine substitution in GPIHBP1 Ly6 domain. Journal of Biological Chemistry, 289(28), 19491-19499
Open this publication in new window or tab >>Multimerization of clycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) and familial chylomicronemia from a serine-to-cysteine substitution in GPIHBP1 Ly6 domain
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2014 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 289, no 28, p. 19491-19499Article in journal (Refereed) Published
Abstract [en]

GPIHBP1, a glycosylphosphatidylinositol-anchored glycoprotein of microvascular endothelial cells, binds lipoprotein lipase (LPL) within the interstitial spaces and transports it across endothelial cells to the capillary lumen. The ability of GPIHBP1 to bind LPL depends on the Ly6 domain, a three-fingered structure containing 10 cysteines and a conserved pattern of disulfide bond formation. Here, we report a patient with severe hypertriglyceridemia who was homozygous for a GPIHBP1 point mutation that converted a serine in the GPIHBP1 Ly6 domain (Ser-107) to a cysteine. Two hypertriglyceridemic siblings were homozygous for the same mutation. All three homozygotes had very low levels of LPL in the preheparin plasma. We suspected that the extra cysteine in GPIHBP1-S107C might prevent the trafficking of the protein to the cell surface, but this was not the case. However, nearly all of the GPIHBP1-S107C on the cell surface was in the form of disulfide-linked dimers and multimers, whereas wild-type GPIHBP1 was predominantly monomeric. An insect cell GPIHBP1 expression system confirmed the propensity of GPIHBP1-S107C to form disulfide-linked dimers and to form multimers. Functional studies showed that only GPIHBP1 monomers bind LPL. In keeping with that finding, there was no binding of LPL to GPIHBP1-S107C in either cell-based or cell-free binding assays. We conclude that an extra cysteine in the GPIHBP1 Ly6 motif results in multimerization of GPIHBP1, defective LPL binding, and severe hypertriglyceridemia.

Place, publisher, year, edition, pages
American Society for Biochemistry and Molecular Biology, 2014
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-91838 (URN)10.1074/jbc.M114.558528 (DOI)000339326800024 ()
Available from: 2014-08-27 Created: 2014-08-18 Last updated: 2018-06-07Bibliographically approved
Larsson, M., Vorrsjö, E., Talmud, P., Lookene, A. & Olivecrona, G. (2013). Apolipoproteins C-I and C-III Inhibit Lipoprotein Lipase Activity by Displacement of the Enzyme from Lipid Droplets. Journal of Biological Chemistry, 288(47), 33997-34008
Open this publication in new window or tab >>Apolipoproteins C-I and C-III Inhibit Lipoprotein Lipase Activity by Displacement of the Enzyme from Lipid Droplets
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2013 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 288, no 47, p. 33997-34008Article in journal (Refereed) Published
Abstract [en]

Apolipoproteins (apo) C-I and C-III are known to inhibit lipoprotein lipase (LPL) activity, but the molecular mechanisms for this remain obscure. We present evidence that either apoC-I or apoC-III, when bound to triglyceride-rich lipoproteins, prevent binding of LPL to the lipid/water interface. This results in decreased lipolytic activity of the enzyme. Site-directed mutagenesis revealed that hydrophobic amino acid residues centrally located in the apoC-III molecule are critical for attachment to lipid emulsion particles and consequently inhibition of LPL activity. Triglyceride-rich lipoproteins stabilize LPL and protect the enzyme from inactivating factors such as angiopoietin-like protein 4 (angptl4). The addition of either apoC-I or apoC-III to triglyceride-rich particles severely diminished their protective effect on LPL and rendered the enzyme more susceptible to inactivation by angptl4. These observations were seen using chylomicrons as well as the synthetic lipid emulsion Intralipid. In the presence of the LPL activator protein apoC-II, more of apoC-I or apoC-III was needed for displacement of LPL from the lipid/water interface. In conclusion, we show that apoC-I and apoC-III inhibit lipolysis by displacing LPL from lipid emulsion particles. We also propose a role for these apolipoproteins in the irreversible inactivation of LPL by factors such as angptl4.

Keywords
Apolipoproteins, Dyslipidemia, Lipolysis, Lipoprotein, Lipoprotein Metabolism, Triglyceride, Apolipoprotein C-I, Apolipoprotein C-III, Lipoprotein Lipase
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-85558 (URN)10.1074/jbc.M113.495366 (DOI)000327250200041 ()
Funder
Swedish Research Council, 12203Swedish Heart Lung Foundation
Available from: 2014-02-07 Created: 2014-02-06 Last updated: 2018-06-08Bibliographically approved
Robal, T., Larsson, M., Martin, M., Olivecrona, G. & Lookene, A. (2012). Fatty acids bind tightly to the N-terminal domain of angiopoietin-like protein 4 and modulate its interaction with lipoprotein lipase. Journal of Biological Chemistry, 287(35), 29739-29752
Open this publication in new window or tab >>Fatty acids bind tightly to the N-terminal domain of angiopoietin-like protein 4 and modulate its interaction with lipoprotein lipase
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2012 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 287, no 35, p. 29739-29752Article in journal (Refereed) Published
Abstract [en]

Angiopoietin-like protein 4 (Angptl4), a potent regulator of plasma triglyceride metabolism, binds to lipoprotein lipase (LPL) through its N-terminal coiled-coil domain (ccd-Angptl4) inducing dissociation of the dimeric enzyme to inactive monomers. In the present study we demonstrate that fatty acids reduce the inactivation of LPL by Angptl4. This was the case both with ccd-Angptl4 and full length Angptl4 and the effect was seen in human plasma or in the presence of albumin. The effect decreased in the sequence oleic acid > palmitic acid > myristic acid >linoleic acid >linolenic acid. Surface plasmon resonance, isothermal titration calorimetry, fluorescence and chromatography measurements revealed that fatty acids bind with high affinity to ccd-Angptl4. The interactions were characterized by fast association and slow dissociation rates, indicating formation of stable complexes. The highest affinity for ccd-Angptl4 was detected for oleic acid with a sub-nanomolar equilibrium dissociation constant (Kd). The Kd values for palmitic and myristic acid were in nanomolar range. Linoleic and linolenic acid bound with much lower affinity. On binding of fatty acids, ccd-Angptl4 underwent conformational changes resulting in a decreased helical content, weakened structural stability, dissociation of oligomers, and altered fluorescence properties of the Trp38 residue which is located close to the putative LPL-binding region. Based on these results, we propose that fatty acids play an important role in modulating the effects of Angptl4.

Place, publisher, year, edition, pages
Bethesda: American Society for Biochemistry and Molecular Biology, 2012
National Category
Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:umu:diva-57336 (URN)10.1074/jbc.M111.303529 (DOI)000308286900050 ()22773878 (PubMedID)
Available from: 2012-07-13 Created: 2012-07-13 Last updated: 2018-06-08Bibliographically approved
Nilsson, S., Anderson, F., Ericsson, M., Larsson, M., Makoveychuk, E., Lookene, A., . . . Olivecrona, G. (2012). Triacylglycerol-rich lipoproteins protect lipoprotein lipase from inactivation by ANGPTL3 and ANGPTL4. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1821(10), 1370-1378
Open this publication in new window or tab >>Triacylglycerol-rich lipoproteins protect lipoprotein lipase from inactivation by ANGPTL3 and ANGPTL4
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2012 (English)In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1879-2618, Vol. 1821, no 10, p. 1370-1378Article in journal (Refereed) Published
Abstract [en]

Lipoprotein lipase (LPL) is important for clearance of triacylglycerols (TG) from plasma both as an enzyme and as a bridging factor between lipoproteins and receptors for endocytosis. The amount of LPL at the luminal side of the capillary endothelium determines to what extent lipids are taken up. Mechanisms to control both the activity of LPL and its transport to the endothelial sites are regulated, but poorly understood. Angiopoietin-like proteins (ANGPTLs) 3 and 4 are potential control proteins for LPL, but plasma concentrations of ANGPTLs do not correlate with plasma TG levels. We investigated the effects of recombinant human N-terminal (NT) ANGPTLs3 and 4 on LPL-mediated bridging of TG-rich lipoproteins to primary mouse hepatocytes and found that the NT-ANGPTLs, in concentrations sufficient to cause inactivation of LPL in vitro, were unable to prevent LPL-mediated lipoprotein uptake. We therefore investigated the effects of lipoproteins (chylomicrons, VLDL and LDL) on the inactivation of LPL in vitro by NT-ANGPTLs3 and 4 and found that LPL activity was protected by TG-rich lipoproteins. In vivo, postprandial TG protected LPL from inactivation by recombinant NT-ANGPTL4 injected to mice. We conclude that lipoprotein-bound LPL is stabilized against inactivation by ANGPTLs. The levels of ANGPTLs found in blood may not be sufficient to overcome this stabilization. Therefore it is likely that the prime site of action of ANGPTLs on LPL is in subendothelial compartments where TG-rich lipoprotein concentration is lower than in blood. This could explain why the plasma levels of TG and ANGPTLs do not correlate.

Place, publisher, year, edition, pages
Amsterdam: Elsevier, 2012
Keywords
ANGPTL3, ANGPTL4, Lipoprotein lipase, Triacylglycerol metabolism, VLDL, Chylomicron
National Category
Other Medical Sciences
Research subject
Medicine
Identifiers
urn:nbn:se:umu:diva-57187 (URN)10.1016/j.bbalip.2012.06.003 (DOI)000308389100008 ()
Available from: 2012-07-10 Created: 2012-07-10 Last updated: 2018-06-08Bibliographically approved
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