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Makoveichuk, Elena
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Publications (10 of 11) Show all publications
Nyrén, R., Makoveichuk, E., Malla, S., Kersten, S., Nilsson, S. K., Ericsson, M. & Olivecrona, G. (2019). Lipoprotein lipase in mouse kidney: effects of nutritional status and high-fat diet. American Journal of Physiology - Renal Physiology, 316(3), F558-F571
Open this publication in new window or tab >>Lipoprotein lipase in mouse kidney: effects of nutritional status and high-fat diet
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2019 (English)In: American Journal of Physiology - Renal Physiology, ISSN 1931-857X, E-ISSN 1522-1466, Vol. 316, no 3, p. F558-F571Article in journal (Refereed) Published
Abstract [en]

Activity of lipoprotein lipase (LPL) is high in mouse kidney, but the reason is poorly understood. The aim was to characterize localization, regulation, and function of LPL in kidney of C57BL/6J mice. We found LPL mainly in proximal tubules, localized inside the tubular epithelial cells, under all conditions studied. In fed mice, some LPL, colocalized with the endothelial markers CD31 and GPIHBP1 and could be removed by perfusion with heparin. indicating a vascular location. The role of angiopoietin-like protein 4 (ANGPTL4) for nutritional modulation of LPL activity was studied in wild-type and Angptl4(-/-) mice. In Angptl4(-/-) mice, kidney LPL activity remained high in fasted animals, indicating that ANGPTL4 is involved in suppression of LPL activity on fasting, like in adipose tissue. The amount of ANGPTL4 protein in kidney was low, and the protein appeared smaller in size, compared with ANGPTL4 in heart and adipose tissue. To study the influence of obesity, mice were challenged with high-fat diet for 22 wk, and LPL was studied after an overnight fast compared with fasted mice given food for 3 h. High-fat diet caused blunting of the normal adaptation of LPL activity to feeding/fasting in adipose tissue, but in kidneys this adaptation was lost only in male mice. LPL activity increases to high levels in mouse kidney after feeding, but as no difference in uptake of chylomicron triglycerides in kidneys is found between fasted and fed states, our data confinn that LPL appears to have a minor role for lipid uptake in this organ.

Place, publisher, year, edition, pages
American Physiological Society, 2019
Keywords
angiopoietin-like protein 4, high-fat diet, lipoprotein lipase, mouse, triglyceride uptake
National Category
Physiology
Identifiers
urn:nbn:se:umu:diva-158108 (URN)10.1152/ajprenal.00474.2018 (DOI)000462008700015 ()30698048 (PubMedID)
Funder
Swedish Research Council, 2015-02942Swedish Heart Lung Foundation, 2016-245-32M
Available from: 2019-04-12 Created: 2019-04-12 Last updated: 2019-04-12Bibliographically approved
Blomquist, C., Chorell, E., Ryberg, M., Mellberg, C., Worrsjö, E., Makoveichuk, E., . . . Olsson, T. (2018). Decreased lipogenesis-promoting factors in adipose tissue in postmenopausal women with overweight on a Paleolithic-type diet. European Journal of Nutrition, 57(8), 2877-2886
Open this publication in new window or tab >>Decreased lipogenesis-promoting factors in adipose tissue in postmenopausal women with overweight on a Paleolithic-type diet
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2018 (English)In: European Journal of Nutrition, ISSN 1436-6207, E-ISSN 1436-6215, Vol. 57, no 8, p. 2877-2886Article in journal (Refereed) Published
Abstract [en]

Purpose: We studied effects of diet-induced postmenopausal weight loss on gene expression and activity of proteins involved in lipogenesis and lipolysis in adipose tissue.

Methods: Fifty-eight postmenopausal women with overweight (BMI 32.5 ± 5.5) were randomized to eat an ad libitum Paleolithic-type diet (PD) aiming for a high intake of protein and unsaturated fatty acids or a prudent control diet (CD) for 24 months. Anthropometry, plasma adipokines, gene expression of proteins involved in fat metabolism in subcutaneous adipose tissue (SAT) and lipoprotein lipase (LPL) activity and mass in SAT were measured at baseline and after 6 months. LPL mass and activity were also measured after 24 months.

Results: The PD led to improved insulin sensitivity (P < 0.01) and decreased circulating triglycerides (P < 0.001), lipogenesis-related factors, including LPL mRNA (P < 0.05), mass (P < 0.01), and activity (P < 0.001); as well as gene expressions of CD36 (P < 0.05), fatty acid synthase, FAS (P < 0.001) and diglyceride acyltransferase 2, DGAT2 (P < 0.001). The LPL activity (P < 0.05) and gene expression of DGAT2 (P < 0.05) and FAS (P < 0.05) were significantly lowered in the PD group versus the CD group at 6 months and the LPL activity (P < 0.05) remained significantly lowered in the PD group compared to the CD group at 24 months.

Conclusions: Compared to the CD, the PD led to a more pronounced reduction of lipogenesis-promoting factors in SAT among postmenopausal women with overweight. This could have mediated the favorable metabolic effects of the PD on triglyceride levels and insulin sensitivity.

Place, publisher, year, edition, pages
Springer, 2018
Keywords
diet, fat metabolism, lipoprotein lipase, obesity, postmenopausal women
National Category
Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-141559 (URN)10.1007/s00394-017-1558-0 (DOI)000450829600020 ()29075849 (PubMedID)
Available from: 2017-11-08 Created: 2017-11-08 Last updated: 2019-05-10Bibliographically approved
Makoveichuk, E., Ruge, T., Nilsson, S., Södergren, A. & Olivecrona, G. (2017). High concentrations of Angiopoietin-like Protein 4 detected in serum from patients with rheumatoid arthritis can be explained by non-specific antibody reactivity. PLoS ONE, 12(1), Article ID e0168922.
Open this publication in new window or tab >>High concentrations of Angiopoietin-like Protein 4 detected in serum from patients with rheumatoid arthritis can be explained by non-specific antibody reactivity
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2017 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 12, no 1, article id e0168922Article in journal (Refereed) Published
Abstract [en]

Angiopoietin-like protein 4 (ANGPTL4) is suggested to be a master regulator of plasma triglyceride metabolism. Our aim was to study whether the previously reported high levels of ANGPTL4 detected in serum from patients with rheumatoid arthritis (RA) by ELISA was due to any specific molecular form of this protein (oligomers, monomers or fragments). ANGPTL4 levels were first determined in serum from 68 RA patients and 43 age and sex matched control subjects and the mean values differed by a factor of 5.0. Then, ANGPTL4 was analyzed after size exclusion chromatography (SEC) of serum samples. With serum from one of the RA patients with high levels of ANGPTL4, the dominant reactivity was found in fractions corresponding to high-molecular weight proteins. In addition, a minor peak of reactivity eluting late from the column was found both in the patient and in controls. By the use of Hetero-Block r, and by careful selection of antibodies, we documented non-specific reactions for ANGPTL4 in 39% of samples from the RA patients, most likely due to cross-reactivity of the antibodies with rheumatoid factor (RF). The corresponding figure for control subjects was 6.3%. After corrections for non-specific reactions, the mean level of ANGPTL4 in serum from RA patients was still significantly higher than in control individuals (mean levels were 101 +/- 62 and 67 +/- 39 ng/ml respectively, P = 0.02). We re-analyzed samples from our previously published studies on ANGPL4 levels in patients on hemodialysis and patients with diabetes type 2. These samples did not show false positive reactions. The levels of ANGPTL4 were comparable to those detected previously.

National Category
Rheumatology and Autoimmunity Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-131869 (URN)10.1371/journal.pone.0168922 (DOI)000392405300017 ()28107351 (PubMedID)
Available from: 2017-02-27 Created: 2017-02-27 Last updated: 2019-05-23Bibliographically approved
Heverin, M., Ali, Z., Olin, M., Tillander, V., Joibari, M. M., Makoveichuk, E., . . . Björkhem, I. (2017). On the regulatory importance of 27-hydroxycholesterol in mouse liver. Journal of Steroid Biochemistry and Molecular Biology, 169, 10-21
Open this publication in new window or tab >>On the regulatory importance of 27-hydroxycholesterol in mouse liver
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2017 (English)In: Journal of Steroid Biochemistry and Molecular Biology, ISSN 0960-0760, E-ISSN 1879-1220, Vol. 169, p. 10-21Article, review/survey (Refereed) Published
Abstract [en]

27-Hydroxycholesterol (27OH) is a strong suppressor of cholesterol synthesis and a weak activator of LXR in vitro. The regulatory importance of 27OH in vivo is controversial. Here we utilized male mice with increased levels of 27OH either due to increased production (CYP27A1 transgenic mice) or reduced metabolism (Cyp7b1-/- mice). We also used mice lacking 27OH due to a knockout of Cyp27a1. The latter mice were treated with cholic acid to compensate for reduced bile acid synthesis. The effects of the different levels of 27OH on Srebp- and other LXR-regulated genes in the liver were investigated. In the liver of CYP27tg mice we found a modest increase of the mRNA levels corresponding to the LXR target genes Cyp7b1 and Abca1. A number of other LXR-regulated genes were not affected. The effect on Abca1 mRNA was not seen in the liver of Cyp7b1-/- mice. There were little or no effects on cholesterol synthesis. In the liver of the Cyp27-/- mice treated with 0.025% cholic acid there was no significant effect of the knockout on the LXR target genes. In a previous work triple-knockout mice deficient in the biosynthesis of 24S-hydroxycholesterol, 25-hydroxycholesterol and 27OH were shown to have impaired response to dietary cholesterol, suggesting side-chain oxidized oxysterols to be mediators in cholesterol-induced effects on LXR target genes at a transcriptional level (Chen W. et al., Cell Metab. 5 (2007) 73-79). The hydroxylated oxysterol responsible for the effect was not defined. We show here that treatment of wildtype mice with dietary cholesterol under the same conditions as in the above study induced the LXR target genes Lpl, Abcg8 and Srebp1c in wild type mice but failed to activate the same genes in mice lacking 27-hydroxycholesterol due to a knockout of Cyp27. We failed to demonstrate the above effects at the protein level (Abcg8) or at the activity level (Lpl). The results suggest that 27OH is not an important regulator of Srebp- or LXR regulated genes under basal conditions in mouse liver. On the other hand 27OH appears to mediate cholesterol-induced effects on some LXR target genes at a transcriptional level under some in vivo conditions. 

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Cholesterol metabolism, Gene expression, Nuclear receptor, OXysterols, Cytochrome P-450, Cyp27-/- mice, Lipoprotein lipase, Abcg8, Srebp1c, Lxr
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-136070 (URN)10.1016/j.jsbmb.2016.02.001 (DOI)000401391300003 ()26851362 (PubMedID)
Note

Special Issue: SI

Available from: 2017-06-16 Created: 2017-06-16 Last updated: 2018-06-09Bibliographically approved
Makoveichuk, E., Vorrsjö, E., Olivecrona, T. & Olivecrona, G. (2017). TNF-alpha decreases lipoprotein lipase activity in 3T3-L1 adipocytes by up-regulation of angiopoietin-like protein 4. Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 1862(5), 533-540
Open this publication in new window or tab >>TNF-alpha decreases lipoprotein lipase activity in 3T3-L1 adipocytes by up-regulation of angiopoietin-like protein 4
2017 (English)In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1879-2618, Vol. 1862, no 5, p. 533-540Article in journal (Refereed) Published
Abstract [en]

Lipoprotein lipase (LPL) hydrolyzes lipids in plasma lipoproteins so that the fatty acids can be taken up and used by cells. The activity of LPL changes rapidly in response to changes in nutrition, physical activity and other conditions. Angiopoietin-like protein 4 (ANGPTL4) is an important controller of LPL activity. Both LPL and ANGPTL4 are produced and secreted by adipocytes. When the transcription blocker Actinomycin D was added to cultures of 3T3-L1 adipocytes, LPL activity in the medium increased several-fold. LPL mRNA decreased moderately during 5 h, while ANGPTL4 mRNA and protein declined rapidly, explaining that LPL activity was increased. TNF-alpha is known to reduce LPL activity in adipose tissue. We have shown that TNF-a increased ANGPTL4 both at the mRNA and protein level. Expression of ANGPTL4 is known to be under control of Foxol. Use of the Foxol-specific inhibitor AS1842856, or knockdown of ANGPTL4 by RNAi, resulted in increased LPL activity in the medium. Both with ActD and with the Foxol inhibitor the cells became unresponsive to TNF-a. This study shows that TNF-a, by a Foxol dependent pathway, increases the transcription of ANGPTL4 which is secreted by the cells and causes inactivation of LPL.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Lipoprotein lipase, TNF-alpha, 3T3-L1 adipocytes, Angiopoietin-like protein 4, Actinomycin D, Foxol inhibitor
National Category
Cell Biology Medicinal Chemistry
Identifiers
urn:nbn:se:umu:diva-136063 (URN)10.1016/j.bbalip.2017.02.005 (DOI)000400715800009 ()28215713 (PubMedID)
Available from: 2017-06-19 Created: 2017-06-19 Last updated: 2018-06-09Bibliographically approved
Zemankova, K., Makoveichuk, E., Vlasakova, Z., Olivecrona, G. & Kovar, J. (2015). Acute alcohol consumption downregulates lipoprotein lipase activity in vivo. Metabolism: Clinical and Experimental, 64(11), 1592-1596
Open this publication in new window or tab >>Acute alcohol consumption downregulates lipoprotein lipase activity in vivo
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2015 (English)In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 64, no 11, p. 1592-1596Article in journal (Refereed) Published
Abstract [en]

Objective. Acute alcohol consumption can induce hypertriglyceridemia. Such an effect could be explained in part by the influence of alcohol on lipoprotein lipase (LPL) - the key enzyme responsible for triglyceride hydrolysis in circulation. Therefore, we have studied the effects of acute moderate alcohol consumption on LPL activity and on the concentrations of angiopoietin-like proteins 3 and 4 (ANGPTL3 and ANGPTL4), which are known to inhibit LPL. Methods. Two experiments were carried out in 8 healthy volunteers. They received 25 g of alcohol (vodka) in one experiment and water in the other (control). The in vivo function of LPL was estimated using intravenous fat tolerance tests (IVFTT) carried out before, 2 and 4 hours after alcohol administration. At the end of each experiment, LPL activity and mass were measured in post-heparin plasma (PHP). The concentrations of ANGPTL3 and ANGPTL4 in blood were measured before alcohol consumption and at the end of the experiments. Results. LPL activity, as estimated using the IVFTT, was reduced by 25% and 24% two and four hours after the administration of alcohol, respectively, and was not affected in the control experiment. At the end of the experiment, LPL activity in PHP was 23% lower after alcohol consumption than in the controls. The concentrations of ANGPTL3 and ANGPTL4 had dropped to 67% and 86% of baseline values, respectively, at 280 min after alcohol consumption. These levels were not affected in the control experiment. The levels of ANGPTL4 but not those of ANGPTL3 were increased in PHP compared to both baseline values and values at 280 min. Conclusion. The capacity for triglyceride clearance seemed to be acutely reduced by alcohol consumption and the effect persisted for several hours. The levels of LPL activity in PHP were reduced to a similar extent. This reduction in LPL activity could not be explained by the changes in the levels of ANGPTL3 or ANGPTL4, which both decreased. (C) 2015 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Lipoprotein lipase, Alcohol, Angiopoietin-like proteins, Triglycerides, Non-esterified fatty acids
National Category
Chemical Sciences
Identifiers
urn:nbn:se:umu:diva-111470 (URN)10.1016/j.metabol.2015.08.016 (DOI)000363437000026 ()26388538 (PubMedID)
Available from: 2015-12-09 Created: 2015-11-13 Last updated: 2018-06-07Bibliographically approved
Makoveichuk, E., Vorrsjö, E., Olivecrona, T. & Olivecrona, G. (2013). Inactivation of lipoprotein lipase in 3T3-L1 adipocytes by angiopoietin-like protein 4 requires that both proteins have reached the cell surface. Biochemical and Biophysical Research Communications - BBRC, 441(4), 941-946
Open this publication in new window or tab >>Inactivation of lipoprotein lipase in 3T3-L1 adipocytes by angiopoietin-like protein 4 requires that both proteins have reached the cell surface
2013 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 441, no 4, p. 941-946Article in journal (Refereed) Published
Abstract [en]

Lipoprotein lipase (LPL) and angiopoietin-like protein 4 (Angptl4) were studied in 3T3-L1 adipocytes. Transfections of the adipocytes with Angptl4 esiRNA caused reduction of the expression of Angptl4 to about one fourth of that in cells treated with vehicle only. This resulted in higher levels of LPL activity both on cell surfaces (heparin-releasable) and in the medium, while LPL activity within the cells remained unaffected. This demonstrated that even though both proteins are made in the same cell, Angptl4 does not inactivate LPL during intracellular transport. Most of the Angptl4 protein was present as covalent dimers and tetramers on cell surfaces, while within the cells there were only monomers. LPL gradually lost activity when incubated in medium, but there was no marked difference between conditioned medium from normal cells (rich in Angptl4) and medium after knockdown of Angptl4. Hence Angptl4 did not markedly accelerate inactivation of LPL in the medium. Experiments with combinations of different cells and media indicated that inactivation of LPL occurred on the surfaces of cells producing Angptl4. (C) 2013 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2013
Keywords
Adipocytes, RNAi, Heparin-releasable, 3T3-L1, Angiopoietin-like protein 4, Lipoprotein lipase
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-84787 (URN)10.1016/j.bbrc.2013.11.013 (DOI)000328434800042 ()
Available from: 2014-01-29 Created: 2014-01-20 Last updated: 2018-06-08Bibliographically approved
Ruge, T., Sukonina, V., Kroupa, O., Makoveichuk, E., Lundgren, M., Svensson, M. K., . . . Eriksson, J. W. (2012). Effects of hyperinsulinemia on lipoprotein lipase, angiopoietinlike protein 4, and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in subjects with and without type 2 diabetes mellitus. Metabolism: Clinical and Experimental, 61(5), 652-660
Open this publication in new window or tab >>Effects of hyperinsulinemia on lipoprotein lipase, angiopoietinlike protein 4, and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in subjects with and without type 2 diabetes mellitus
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2012 (English)In: Metabolism: Clinical and Experimental, ISSN 0026-0495, E-ISSN 1532-8600, Vol. 61, no 5, p. 652-660Article in journal (Refereed) Published
Abstract [en]

Our aims were to compare the systemic effects of insulin on lipoprotein lipase (LPL) in tissues from subjects with different degrees of insulin sensitivity. The effects of insulin on LPL during a 4-hour hyperinsulinemic, euglycemic clamp were studied in skeletal muscle, adipose tissue, and postheparin plasma from young healthy subjects (YS), older subjects with type 2 diabetes mellitus (DS), and older control subjects (CS). In addition, we studied the effects of insulin on the expression of 2 recently recognized candidate genes for control of LPL activity: angiopoietin-like protein 4 (ANGPTL4) and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1. As an effect of insulin, LPL activity decreased by 20% to 25% in postheparin plasma and increased by 20% to 30% in adipose tissue in all groups. In YS, the levels of ANGPTL4 messenger RNA in adipose tissue decreased 3-fold during the clamp. In contrast, there was no significant change in DS or CS. Regression analysis showed that the ability of insulin to reduce the expression of ANGPTL4 was positively correlated with M-values and inversely correlated with factors linked to the metabolic syndrome. Expression of glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 tended to be higher in YS than in DS or CS, but the expression was not affected by insulin in any of the groups. Our data imply that the insulin-mediated regulation of LPL is not directly linked to the control of glucose turnover by insulin or to ANGPTL4 expression in adipose tissue or plasma. Interestingly, the response of ANGPTL4 expression in adipose tissue to insulin was severely blunted in both DS and CS. (C) 2012 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2012
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-56230 (URN)10.1016/j.metabol.2011.09.014 (DOI)000303617600007 ()
Available from: 2012-06-14 Created: 2012-06-12 Last updated: 2018-06-08Bibliographically approved
Makoveichuk, E., Sukonina, V., Kroupa, O., Thulin, P., Ehrenborg, E., Olivecrona, T. & Olivecrona, G. (2012). Inactivation of lipoprotein lipase occurs on the surface of THP-1 macrophages where oligomers of angiopoietin-like protein 4 are formed. Biochemical and Biophysical Research Communications - BBRC, 425(2), 138-143
Open this publication in new window or tab >>Inactivation of lipoprotein lipase occurs on the surface of THP-1 macrophages where oligomers of angiopoietin-like protein 4 are formed
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2012 (English)In: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 425, no 2, p. 138-143Article in journal (Refereed) Published
Abstract [en]

Lipoprotein lipase (LPL) hydrolyzes triglycerides in plasma lipoproteins causing release of fatty acids for metabolic purposes in muscles and adipose tissue. LPL in macrophages in the artery wall may, however, promote foam cell formation and atherosclerosis. Angiopoietin-like protein (ANGPTL) 4 inactivates LPL and ANGPTL4 expression is controlled by peroxisome proliferator-activated receptors (PPAR). The mechanisms for inactivation of LPL by ANGPTL4 was studied in THP-1 macrophages where active LPL is associated with cell surfaces in a heparin-releasable form, while LPL in the culture medium is mostly inactive. The PPAR delta agonist GW501516 had no effect on LPL mRNA, but increased ANGPTL4 mRNA and caused a marked reduction of the heparin-releasable LPL activity concomitantly with accumulation of inactive, monomeric LPL in the medium. Intracellular ANGPTL4 was monomeric, while dimers and tetramers of ANGPTL4 were present in the heparin-releasable fraction and medium. GW501516 caused an increase in the amount of ANGPTL4 oligomers on the cell surface that paralleled the decrease in LPL activity. Actinomycin D blocked the effects of GW501516 on ANGPTL4 oligomer formation and prevented the inactivation of LPL Antibodies against ANGPTL4 interfered with the inactivation of LPL. We conclude that inactivation of LPL in THP-1 macrophages primarily occurs on the cell surface where oligomers of ANGPTL4 are formed. (c) 2012 Elsevier Inc. All rights reserved.

Place, publisher, year, edition, pages
San Diego: Elsevier, 2012
Keywords
Angiopoietin-like protein 4, Lipoprotein lipase, Macrophages, GW501516
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-60081 (URN)10.1016/j.bbrc.2012.07.048 (DOI)000308384400004 ()
Available from: 2012-10-08 Created: 2012-10-01 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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