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  • 1.
    Chevreuil, O
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hultin, M
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Ostergaard, P
    Olivecrona, T
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Biphasic effects of low-molecular-weight and conventional heparins on chylomicron clearance in rats.1993Inngår i: Arteriosclerosis and thrombosis : a journal of vascular biology / American Heart Association, ISSN 1049-8834, Vol. 13, nr 10, s. 1397-403Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chylomicrons labeled in vivo with [14C]triglycerides and [3H]retinyl esters were injected in rats at a series of times after administration of conventional unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or saline. In saline controls the clearance of both chylomicron triglycerides and retinyl esters seemed to follow exponential courses, with half-lives of about 5 and 10 minutes, respectively. Five minutes after administration of LMWH or UFH, the triglyceride clearance rates were dramatically increased and were associated with an increased appearance of the radiolabel in circulating free fatty acids (FFAs). The clearance of [3H]retinol radioactivity, ie, chylomicron particles, was also enhanced 5 minutes after heparin injection. From 75% to 90% disappeared from the circulation within the first 5 minutes. Their continued disappearance was much slower, with a slope similar to that of the saline-treated rats. Hence, it was as if a new, rapid exponent had been added to the disappearance curve that accounted for most of the particle clearance. Injection of chylomicrons 1 hour after the heparins resulted in substantially slower clearance compared with saline-treated controls of both triglyceride and retinol radioactivity in rats given a high dose of LMWH or a low dose of either heparin. Appearance of label in plasma FFAs was also decreased, suggesting that impeded lipolysis was responsible, at least in part, for the impeded chylomicron clearance. Four and 24 hours after heparin injection all studied parameters of chylomicron clearance had returned to normal.(ABSTRACT TRUNCATED AT 250 WORDS)

  • 2.
    Chevreuil, O
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hultin, M
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Ostergaard, P
    Olivecrona, T
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Depletion of lipoprotein lipase after heparin administration.1993Inngår i: Arteriosclerosis and thrombosis : a journal of vascular biology / American Heart Association, ISSN 1049-8834, Vol. 13, nr 10, s. 1391-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Some or most of the turnover of lipoprotein lipase (LPL) occurs by dissociation from vascular endothelial sites in extrahepatic tissues and further degradation in the liver. Heparin greatly enhances this dissociation and delays but does not abolish uptake in the liver, raising the possibility that heparin could lead to accelerated catabolism of functional LPL. To investigate this, we determined time curves for heparin (anti-factor Xa activity) and for LPL and hepatic lipase after injection in rats of two doses of conventional unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). The high dose (250 U/kg) of both heparins resulted in similar initial levels of LPL activity in plasma, but at 30 minutes the activity with LMWH had declined by more than 80%, whereas with UFH it remained essentially unchanged during this time. In contrast, time curves for heparin activity in blood were similar for the two heparins. The low dose (50 U/kg) led to lower initial levels of LPL activity with LMWH in spite of slower elimination of heparin activity from the blood. These results agree with previous studies that indicate that LMWH has a similar ability as UFH to release LPL, but a lesser ability to delay its removal by the liver. Only slight differences were noted in the time curves for hepatic lipase with the two heparins. To assess the possible depletion of the lipases, we administered a second large dose of conventional heparin. One hour after the first injection, the second injection resulted in lower plasma LPL activities in all four groups.(ABSTRACT TRUNCATED AT 250 WORDS)

  • 3.
    Chevreuil, O
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hultin, M
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Ostergaard, P
    Olivecrona, T
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Heparin-decasaccharides impair the catabolism of chylomicrons.1996Inngår i: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 320 ( Pt 2), s. 437-44Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    On intravenous injection to rats, decasaccharides gave rise to a short-lived peak of lipoprotein lipase (LPL) activity, whereas octa- and hexasaccharides caused only marginal increases. In isolated hearts perfused by a single pass, decasaccharides released LPL more efficiently than conventional heparin on a mass basis. Octa- and hexasaccharides were much less efficient. Similar results were obtained for hepatic lipase, which was studied both in vivo and by liver perfusion. In the intact rat, the heparin fragments themselves disappeared rapidly from the circulating blood. The decay of hepatic lipase activity after the early peak roughly paralleled the decay of decasaccharide concentration, but for LPL the decay was faster, presumably because the liver extracted this lipase from plasma. To assess the lipase activities remaining in contact with blood a large dose of conventional heparin was injected at a series of times after the decasaccharides. LPL was decreased by 40% after 1 h. At that time, the LPL activity that could be released from isolated hearts by single-pass perfusion with heparin for 2 min ("functional LPL') was decreased by 75%. Chylomicrons labelled in vivo with [14C]oleic acid (primarily in triacylglycerols, providing a tracer for lipolysis) and [3H]retinol (primarily in ester form, providing a tracer for the particles) were injected intravenously to explore the effects of the LPL depletion on lipoprotein metabolism. Triacylglycerol lipolysis and particle clearance was markedly delayed from 30 min to 2 h after injection of decasaccharides. After 1 h the fractional catabolic rate was only one-third of the control value and the catabolism of chylomicron triacylglycerols by perfused hearts was delayed to a similar extent. Thus injection of decasaccharides leads to accelerated turnover of LPL with loss of functional LPL from extrahepatic tissues. This in turn leads to a period of delayed lipolysis and removal of chylomicron particles.

  • 4.
    Eriksson, Jan. W.
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Burén, Jonas
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Svensson, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Postprandial regulation of blood lipids and adipose tissue lipoprotein lipase in type 2 diabetes patients and healthy control subjects2003Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 166, nr 2, s. 359-367Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background/aim: In type 2 diabetes and other insulin-resistant conditions, postprandial hypertriglyceridaemia is an important metabolic perturbation. To further elucidate alterations in the clearance of triglyceride-rich lipoproteins in type 2 diabetes we focused on the nutritional regulation of adipose tissue lipoprotein lipase (LPL).

    Subjects and methods: Eight subjects with type 2 diabetes and eight age-, sex- and body mass index (BMI)-matched control subjects underwent subcutaneous abdominal adipose tissue biopsies in the fasting state and 3.5 h following a standardized lipid-enriched meal. LPL activity and mass were measured in adipose tissue and also in plasma after an intravenous injection of heparin.

    Results: Postprandial, but not fasting, triglycerides were significantly higher in the diabetic subjects than in the control subjects (3.0±0.4 vs 2.0±0.2 mmol/l, P=0.028). Adipose tissue LPL activity was increased following the meal test by ∼35–55% (P=0.021 and 0.004, respectively). There was no significant difference between the groups in this respect. The specific enzyme activity of LPL was not altered in the postprandial state. Fasting and postprandial adipose tissue LPL activity as well as post-heparin plasma LPL activity tended to be lower among the diabetes patients (NS). There was a significant and independent inverse association between insulin resistance (homeostasis model assessment insulin resistance (HOMA-IR) index) vs post-heparin plasma LPL activity and postprandial triglyceride levels, respectively. Adipose tissue LPL activity was related to insulin action in vitro on adipocyte glucose transport, but not to HOMA-IR.

    Conclusion: Following food intake adipose tissue LPL activity is enhanced to a similar degree in patients with type 2 diabetes and in healthy control subjects matched for BMI, age and gender. If LPL dysregulation is involved in the postprandial hypertriglyceridaemia found in type 2 diabetes, it should occur in tissues other than subcutaneous fat.

  • 5.
    Hultin, M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Bengtsson-Olivecrona, G
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, T
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Release of lipoprotein lipase to plasma by triacylglycerol emulsions. Comparison to the effect of heparin.1992Inngår i: Biochimica et Biophysica Acta, ISSN 0006-3002, E-ISSN 1878-2434, Vol. 1125, nr 1, s. 97-103Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    It was previously known that lipoprotein lipase (LPL) activity in plasma rises after infusion of a fat emulsion. To explore the mechanism we have compared the release of LPL by emulsion to that by heparin. After bolus injections of a fat emulsion (Intralipid) to rats, plasma LPL activity gradually rose 5-fold to a maximum at 6-8 min. During the same time the concentration of injected triacylglycerols (TG) decreased by about half. Hence, the time-course for plasma LPL activity was quite different from that for plasma TG. The disappearance of injected 125I-labelled bovine LPL from circulation was retarded by emulsion. This effect was more marked 30 min than 3 min after injection of the emulsion. The data indicate that the release of LPL into plasma is not solely due to binding of the lipase to the emulsion particles as such, but involves metabolism of the particles. Emulsion increased the fraction of labelled LPL found in adipose tissue, heart and the red muscle studied, but had no significant effect on the fraction found in liver. The effects of emulsion were quite different from those of heparin, which caused an immediate release of the lipase to plasma, decreased uptake of LPL in most extrahepatic tissues by 60-95%, and increased the fraction taken up in the liver.

  • 6.
    Hultin, M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Carneheim, C
    Rosenqvist, K
    Olivecrona, T
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Intravenous lipid emulsions: removal mechanisms as compared to chylomicrons.1995Inngår i: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 36, nr 10, s. 2174-84Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We have compared the metabolism of chylomicrons and a labeled emulsion, similar to those used for parenteral nutrition. Both were labeled in their triglyceride moieties and by a core label. It is known that chylomicron triglycerides are cleared by two processes: removal of triglycerides from the particles through lipolysis and removal of whole or partly lipolyzed particles. It has been proposed that emulsion droplets are cleared by the same pathways. After intravenous injection to postprandial rats, triglycerides were cleared less rapidly from the emulsion than from the chylomicrons (half-lives of 6.4 and 4.0 min), whereas the core labels were cleared at the same rate (half-lives around 7.5 min). This suggests that there was less lipolysis of the emulsion droplets which was further supported by the finding that less label appeared in the plasma free fatty acids (FFA). In adipose tissue of fed rats given chylomicrons, the ratio between fatty acid and core label was above 6, showing that fatty acids had been taken up after lipoprotein lipase-mediated hydrolysis. In contrast, for rats given emulsion, that ratio was only 1.2 showing that nearly as much emulsion droplets as emulsion-derived fatty acids were present in the tissue. In the liver the ratio was 0.55 after chylomicrons but 0.93 after emulsion. In further support of more lipolysis, fatty acids were oxidized more rapidly from chylomicrons than from emulsion. These data suggest that a large fraction of the emulsion droplets was removed from plasma with little or no preceding lipolysis. A substantial proportion, more than 50%, of this uptake occurred in extrahepatic tissues.

  • 7.
    Hultin, M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Müllertz, A
    Zundel, M A
    Olivecrona, G
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hansen, T T
    Deckelbaum, R J
    Carpentier, Y A
    Olivecrona, T
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Metabolism of emulsions containing medium- and long-chain triglycerides or interesterified triglycerides.1994Inngår i: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 35, nr 10, s. 1850-60Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    This study compares the clearing and metabolism of three different lipid emulsions. They had the same phospholipid emulsifier and similar particle sizes. In one (LLL) the core component was long-chain triglycerides (TG), the second (MMM/LLL) contained equal molar amounts of medium- and long-chain TG, the third (MLM) contained synthetic TG with medium-chain (M) fatty acids in the 1,3-positions and a long-chain (L) fatty acid in the 2-position. In model experiments with bovine lipoprotein lipase, the MMM component was hydrolyzed preferentially in the MMM/LLL emulsion so that the initial products were M fatty acids and M monoglycerides. The MLM emulsion, in contrast, gave M fatty acids and formation of L-MG (monoglyceride) throughout hydrolysis. For in vivo studies [3H]oleic acid was incorporated into the emulsion TG as marker for the long-chain component. After bolus injection to rats, the MMM/LLL and MLM emulsions were cleared more rapidly than the LLL emulsion. This was true at all TG loads studied (4-64 mg for a 200 g rat). The labeled oleic acid was oxidized somewhat more rapidly when administered in the MLM emulsion compared to the MMM/LLL emulsion. There were only slight differences in tissue distribution of label. Hence, differences in in vivo metabolism of the long-chain fatty acids were small compared to the marked differences in TG structure and in patterns of product release during in vitro lipolysis.

  • 8.
    Hultin, M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, G
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, T
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Effect of protamine on lipoprotein lipase and hepatic lipase in rats.1994Inngår i: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 304 ( Pt 3), s. 959-66Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The polycation protamine impedes the catabolism of triglyceride-rich lipoproteins and this has been suggested to be due to intravascular inactivation of lipoprotein lipase. We have made intravenous injections of protamine to rats and found that both lipoprotein lipase and hepatic lipase activities were released to plasma. The effect of protamine was more short-lived than that obtained by injection of heparin. The release of hepatic lipase by protamine was as effective as the release by heparin, while the amount of lipoprotein lipase released by protamine was only about one-tenth of that released by heparin. This was not due to inactivation of lipoprotein lipase, since injection of an excess of heparin 10 min after injection of protamine released as much lipoprotein lipase activity to plasma as in controls. The results in vivo differed from those obtained in model experiments in vitro. Protamine was able to almost quantitatively release both lipoprotein lipase and hepatic lipase from columns of heparin-agarose. The displacement was dependent on the total amount of protamine that had passed over the column, indicating that it was due to occupation by protamine of all available binding sites. Our results in vivo showed that the binding sites for lipoprotein lipase were not blocked as efficiently as those for hepatic lipase, indicating that the binding structures were not identical. It was concluded that the impaired turnover of lipoproteins by protamine probably was due to prevention of binding of the lipoproteins to endothelial cell surfaces rather than to impaired lipase function.

  • 9.
    Hultin, M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, T
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Conversion of chylomicrons into remnants.1998Inngår i: Atherosclerosis, ISSN 0021-9150, E-ISSN 1879-1484, Vol. 141 Suppl 1, s. S25-9Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The turnover of chylomicrons in the blood is the sum of several processes. The native chylomicron is synthesized in the intestine out of available substrates. When the chylomicron enters the circulation exchanges of apolipoproteins with other lipoproteins, it also binds to the vascular endothelium where the chylomicron is lipolyzed by lipoprotein lipase. After a short period in the circulation the chylomicron/chylomicron remnant appears to be available for receptor mediated uptake. In this paper several of the processes involved in generation and clearance of chylomicron remnants are discussed.

  • 10.
    Hultin, M
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Savonen, R
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, T
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Chylomicron metabolism in rats: lipolysis, recirculation of triglyceride-derived fatty acids in plasma FFA, and fate of core lipids as analyzed by compartmental modelling.1996Inngår i: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 37, nr 5, s. 1022-36Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chylomicrons labeled in vivo with [14C]oleic acid (primarily in triglycerides (TG), providing a tracer for lipolysis) and [3H]retinol (primarily in ester form, providing a tracer for the corelipids) were injected into rats. Disappearance of the two labels from plasma and appearance of label in plasma free fatty acids (FFA) were analyzed by compartmental modelling. Both core and TG label distributed into an apparent volume 10-15% larger than the blood volume. Part of this probably represents margination to endothelial-binding-lipolysis sites. An open two-compartmental model for plasma FFA was derived from experiments where unesterified oleic acid complexed to albumin was injected. Applying this model revealed that most of the oleic acid from chylomicron triglycerides mixes with the FFA. The disappearance of chylomicron core label required a model in which the label transfers into a second compartment before it leaves the blood. The rate constant for the transformation was high and predicted that, on average, chylomicron spent less than 2 min in the first compartment. The rate out from the second compartment predicted that about 60% of the core label left blood while, on average, chylomicron retained more than half of its triglyceride molecules, i.e., after rather limited lipolysis. The mechanism by which the core label leaves blood is not clear. Modelling showed that under the assumption that the process is shared by chylomicron triglycerides, about half of them go out by this pathway. Comparing fed and fasted rats, the main differences were in the turnover of FFA and in the extent to which chylomicron TG label reappeared in the FFA. This study indicates that a large fraction of the triglycerides in chylomicrons leave plasma together with the core lipids and that most of the fatty acids from chylomicron triglycerides mix into the same metabolic compartments as do plasma free fatty acids.

  • 11.
    Hultin, Magnus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi. Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Anestesiologi och intensivvård.
    Savonen, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Chevreuil, Olivier
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Chylomicron metabolism in rats: kinetic modeling indicates that the particles remain at endothelial sites for minutes2013Inngår i: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 54, nr 10, s. 2595-2605Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Chylomicrons labeled in vivo with (14)C-oleic acid (primarily in triglycerides, providing a tracer for lipolysis) and (3)H-retinol (primarily in ester form, providing a tracer for the core lipids) were injected into rats. Radioactivity in tissues was followed at a series of times up to 40 min and the data were analyzed by compartmental modeling. For heart-like tissues it was necessary to allow the chylomicrons to enter into a compartment where lipolysis is rapid and then transfer to a second compartment where lipolysis is slower. The particles remained in these compartments for minutes and when they returned to blood they had reduced affinity for binding in the tissue. In contrast, the data for liver could readily be fitted with a single compartment for native and lipolyzed chylomicrons in blood, and there was no need for a pathway back to blood. A composite model was built from the individual tissue models. This whole-body model could simultaneously fit all data for both fed and fasted rats and allowed estimation of fluxes and residence times in the four compartments; native and lipolyzed chylomicrons ("remnants") in blood, and particles in the tissue compartments where lipolysis is rapid and slow, respectively.

  • 12.
    Karpe, F
    et al.
    Karolinska Institutet.
    Olivecrona, T
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hamsten, A
    Karolinska Institutet.
    Hultin, M
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Chylomicron/chylomicron remnant turnover in humans: evidence for margination of chylomicrons and poor conversion of larger to smaller chylomicron remnants.1997Inngår i: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 38, nr 5, s. 949-61Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The size of cholesterol-rich lipoprotein particles is a strong determinant of whether they may be deposited in the arterial wall and by this become potentially atherogenic. This study deals with the in vivo transformation of larger-sized chylomicrons and chylomicron remnants to smaller-sized remnants. Twelve healthy men aged 22 to 45 years were given a fatty meal to which retinyl palmitate (RP) had been added. Plasmapheresis was performed 4 1/2 h after meal intake to isolate approximately 400 ml plasma. The RP-rich plasma was re-injected to the subject 24 h later. The RP content was determined in whole plasma and in Svedberg flotation rate fractions (Sf) > 400, Sf 60-400 and Sf 20-60. A compartmental model was developed for the kinetic analysis. Lipoprotein fractions showed minimal signs of aggregation, thus arguing for well-preserved postprandial lipoproteins. Approximately a fourth [23% (4-68%)] of the RP-containing lipoproteins in the Sf > 400 pool was converted to smaller species (Sf 60-400). Conversion of material from the Sf 60-400 to the Sf 20-60 fraction could not be detected. In a second study a large bolus dose of a triglyceride emulsion (Intralipid) was injected to subjects shortly after the RP-labeled plasma to investigate the endothelial binding of the chylomicron/chylomicron remnants. RP material in the Sf > 400 fraction rapidly returned to plasma, arguing for margination of chylomicrons, whereas the corresponding effect was minimal in the Sf 60-400 and Sf 20-60 fractions. The formation of small chylomicron remnants from the larger chylomicron/chylomicron remnant species is limited and large chylomicron/chylomicron remnants are not evenly distributed in plasma, rather they show signs of being marginated to the vascular endothelium.

  • 13.
    Kroupa, Olessia
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Vorrsjö, Evelina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Stienstra, Rinke
    Nutrition, Metabolism and Genomics group, Division of Human Nutrition, Wageningen University, Wageningen, 6700EV, The Netherlands.
    Mattijssen, Frits
    Nutrition, Metabolism and Genomics group, Division of Human Nutrition, Wageningen University, Wageningen, 6700EV, The Netherlands.
    Nilsson, Stefan K
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Sukonina, Valentina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap. Department of Medicine, University of Gothenburg, Gothenburg, SE-405 30, Sweden.
    Kersten, Sander
    Nutrition, Metabolism and Genomics group, Division of Human Nutrition, Wageningen University, Wageningen, 6700EV, The Netherlands.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Linking nutritional regulation of Angptl4, Gpihbp1, and Lmf1 to lipoprotein lipase activity in rodent adipose tissue.2012Inngår i: BMC physiology, ISSN 1472-6793, Vol. 12, s. 13-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Lipoprotein lipase (LPL) hydrolyzes triglycerides in lipoproteins and makes fatty acids available for tissue metabolism. The activity of the enzyme is modulated in a tissue specific manner by interaction with other proteins. We have studied how feeding/fasting and some related perturbations affect the expression, in rat adipose tissue, of three such proteins, LMF1, an ER protein necessary for folding of LPL into its active dimeric form, the endogenous LPL inhibitor ANGPTL4, and GPIHBP1, that transfers LPL across the endothelium.

    RESULTS: The system underwent moderate circadian oscillations, for LPL in phase with food intake, for ANGPTL4 and GPIHBP1 in the opposite direction. Studies with cycloheximide showed that whereas LPL protein turns over rapidly, ANGPTL4 protein turns over more slowly. Studies with the transcription blocker Actinomycin D showed that transcripts for ANGPTL4 and GPIHBP1, but not LMF1 or LPL, turn over rapidly. When food was withdrawn the expression of ANGPTL4 and GPIHBP1 increased rapidly, and LPL activity decreased. On re-feeding and after injection of insulin the expression of ANGPTL4 and GPIHBP1 decreased rapidly, and LPL activity increased. In ANGPTL4(-/-) mice adipose tissue LPL activity did not show these responses. In old, obese rats that showed signs of insulin resistance, the responses of ANGPTL4 and GPIHBP1 mRNA and of LPL activity were severely blunted (at 26 weeks of age) or almost abolished (at 52 weeks of age).

    CONCLUSIONS: This study demonstrates directly that ANGPTL4 is necessary for rapid modulation of LPL activity in adipose tissue. ANGPTL4 message levels responded very rapidly to changes in the nutritional state. LPL activity always changed in the opposite direction. This did not happen in Angptl4(-/-) mice. GPIHBP1 message levels also changed rapidly and in the same direction as ANGPTL4, i.e. increased on fasting when LPL activity decreased. This was unexpected because GPIHBP1 is known to stabilize LPL. The plasticity of the LPL system is severely blunted or completely lost in insulin resistant rats.

  • 14.
    Liu, G
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hultin, M
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Ostergaard, P
    Olivecrona, T
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Interaction of size-fractionated heparins with lipoprotein lipase and hepatic lipase in the rat.1992Inngår i: Biochemical Journal, ISSN 0264-6021, E-ISSN 1470-8728, Vol. 285 ( Pt 3), s. 731-6Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Heparin and heparin partially depolymerized by enzymic digestion were separated into six size fractions. Hep 1 (tetrasaccharides), with a mean M(r) of 1200, did not release significant amounts of either lipoprotein lipase (LPL) or hepatic lipase (HL) on intravenous injection into rats. Hep 2 (mainly octa- and deca-saccharides), with a mean M(r) of 2400-3000, released both lipases. To evoke the same plasma activity of LPL and HL required about 10 times more by weight, or about 40 times more molecules, of this heparin than of hep 5 (mean M(r) 12,000, similar to conventional heparin). Hep 5 impeded binding and degradation of 125I-labelled bovine LPL by perfused rat livers. In contrast, hep 2 had no detectable effect on these processes. This demonstrates a difference between the sites in the liver that mediate binding, uptake and degradation of LPL, and the extrahepatic sites that bind functional LPL, and the hepatic sites that bind functional HL. After injection of 3.25 mg of hep 5/kg body weight, plasma LPL activity rapidly rose and then remained high for at least 1 h. With hep 2, plasma LPL also rose rapidly, but then decreased to almost basal by 1 h. When a labelled triacylglycerol emulsion was injected 1 h after the heparins, the fractional catabolic rate was enhanced in the rats that had received conventional heparin, as expected from the high plasma LPL activity, but decreased compared with controls in rats that had received hep 2, indicating that available LPL had been depleted through enhanced transport to and uptake in the liver.

  • 15.
    Mahmood, Dana
    et al.
    Department of Internal Medicine, County Hospital in Östersund.
    Grubbström, Maria
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lundberg, Lennart DI
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Stegmayr, Bernd G
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lipoprotein lipase responds similarly to tinzaparin as to conventional heparin during hemodialysis2010Inngår i: BMC Nephrology, ISSN 1471-2369, E-ISSN 1471-2369, Vol. 11, artikkel-id 33Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Low molecular weight (LMW) heparins are used for anticoagulation during hemodialysis (HD). Studies in animals have shown that LMW-heparins release lipoprotein lipase (LPL) as efficiently as unfractionated (UF) heparin, but are less able to retard hepatic uptake of the lipase. This raises a concern that the LPL system may become exhausted by LMW-heparin in patients on HD. We have explored this in the setting of clinical HD.

    Methods: Twenty patients on chronic hemodialysis were switched from a primed infusion of UF-heparin to a single bolus of tinzaparin. There were long term follow up of variables for the estimation of dialysis efficacy as well as of the LPL release during dialysis and the subsequent impact on the triglycerides.

    Results: The LPL activity in blood was higher on tinzaparin at 40 but lower at 180 minutes during HD. These values did not change during the 6 month study period. There were significant correlations between the LPL activities in individual patients at the beginning and end of the 6 month study period and between the activities on UF-heparin and on tinzaparin, indicating that tissue LPL was not being exhausted. Triglycerides were higher during the HD-session with tinzaparin than UF-heparin. The plasma lipid/lipoprotein levels did not change during the 6 month study period, nor during a 2-year follow up after the switch from UF-heparin to tinzaparin. Urea reduction rate and Kt/V were reduced by 4 and 7% after 6 months with tinzaparin.

    Conclusion: Our data demonstrate that repeated HD with UF-heparin or tinzaparin does not exhaust the LPL-system.

  • 16.
    Makoveichuk, Elena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Sukonina, Valentina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Kroupa, Olessia
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Thulin, Petra
    Ehrenborg, Ewa
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Inactivation of lipoprotein lipase occurs on the surface of THP-1 macrophages where oligomers of angiopoietin-like protein 4 are formed2012Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 425, nr 2, s. 138-143Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 17.
    Makoveichuk, Elena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Vorrsjö, Evelina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Inactivation of lipoprotein lipase in 3T3-L1 adipocytes by angiopoietin-like protein 4 requires that both proteins have reached the cell surface2013Inngår i: Biochemical and Biophysical Research Communications - BBRC, ISSN 0006-291X, E-ISSN 1090-2104, Vol. 441, nr 4, s. 941-946Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 18.
    Makoveichuk, Elena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Vorrsjö, Evelina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    TNF-alpha decreases lipoprotein lipase activity in 3T3-L1 adipocytes by up-regulation of angiopoietin-like protein 42017Inngår i: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1879-2618, Vol. 1862, nr 5, s. 533-540Artikkel i tidsskrift (Fagfellevurdert)
    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.

  • 19.
    Nyrén, Rakel
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Chang, Chuchun L
    Columbia University.
    Lindström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Histologi med cellbiologi.
    Barmina, Anastasia
    Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
    Vorrsjö, Evelina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Ali, Yusuf
    Karolinska Institutet.
    Juntti-Berggren, Lisa
    Karolinska Institutet.
    Bensadoun, André
    Cornell University, Ithaca.
    Young, Stephen G
    University of California, Los Angeles.
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Localization of lipoprotein lipase and GPIHBP1 in mouse pancreas: effects of diet and leptin deficiency2012Inngår i: BMC Physiology, ISSN 1472-6793, E-ISSN 1472-6793, Vol. 12, s. 14-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Lipoprotein lipase (LPL) hydrolyzes triglycerides in plasma lipoproteins and enables uptake of lipolysis products for energy production or storage in tissues. Our aim was to study the localization of LPL and its endothelial anchoring protein glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) in mouse pancreas, and effects of diet and leptin deficiency on their expression patterns. For this, immunofluorescence microscopy was used on pancreatic tissue from C57BL/6 mouse embryos (E18), adult mice on normal or high-fat diet, and adult ob/ob-mice treated or not with leptin. The distribution of LPL and GPIHBP1 was compared to insulin, glucagon and CD31. Heparin injections were used to discriminate between intracellular and extracellular LPL.

    RESULTS: In the exocrine pancreas LPL was found in capillaries, and was mostly co-localized with GPIHBP1. LPL was releasable by heparin, indicating localization on cell surfaces. Within the islets, most of the LPL was associated with beta cells and could not be released by heparin, indicating that the enzyme remained mostly within cells. Staining for LPL was found also in the glucagon-producing alpha cells, both in embryos (E18) and in adult mice. Only small amounts of LPL were found together with GPIHBP1 within the capillaries of islets. Neither a high fat diet nor fasting/re-feeding markedly altered the distribution pattern of LPL or GPIHBP1 in mouse pancreas. Islets from ob/ob mice appeared completely deficient of LPL in the beta cells, while LPL-staining was normal in alpha cells and in the exocrine pancreas. Leptin treatment of ob/ob mice for 12 days reversed this pattern, so that most of the islets expressed LPL in beta cells.

    CONCLUSIONS: We conclude that both LPL and GPIHBP1 are present in mouse pancreas, and that LPL expression in beta cells is dependent on leptin.

  • 20.
    Näsström, Birgit
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Stegmayr, Bernd G.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Lipoprotein lipase during continuous heparin infusion: Tissue stores become partially depleted2001Inngår i: Journal of Laboratory and Clinical Medicine, ISSN 1931-5244, E-ISSN 1878-1810, Vol. 138, nr 3, s. 206-213Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lipoprotein lipase (LPL) and hepatic lipase (HL) are located at vascular surfaces in extrahepatic tissues and in the liver, respectively. Heparin displaces the enzymes into the circulating blood. Animal studies have shown that the liver takes up and degrades LPL. To explore whether heparin leads to a depletion of tissue stores, we followed the lipase activities in plasma during an 8-hour primed infusion of heparin in 10 healthy subjects. After an initial peak, the HL activity decreased slowly after a time curve similar to that for activated partial thromboplastin time. The time curve for LPL was different. After the initial peak, the activity dropped by almost 80%, from 30 to 120 minutes, and then leveled off to a plateau that corresponded to about 15% of the peak level. A second bolus of heparin was given to 4 subjects after 4 hours. The plasma LPL activity increased, but only to about 35% of the original peak level. We conclude that when heparin releases LPL into plasma, the lipase becomes liable to be taken up and degraded by the liver. After less than 1 hour, the stores of LPL have been exhausted, and recruitment of lipase into plasma depends on a slow but stable delivery of newly synthesized molecules.

  • 21.
    Näsström, Birgit
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Stegmayr, Bernd G
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Lipoprotein lipase during heparin infusion: lower activity in hemodialysis patients2003Inngår i: Scandinavian Journal of Clinical and Laboratory Investigation, ISSN 0036-5513, E-ISSN 1502-7686, Vol. 63, nr 1, s. 45-53Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: [corrected] Patients on hemodialysis often have a moderate hypertriglyceridemia in combination with low HDL cholesterol. A contributing factor may be a derangement of the lipoprotein lipase (LPL) system. During dialysis, with heparin as anticoagulant, the enzyme is released into the circulating blood. METHODS: We have followed LPL activity and triglycerides during ordinary heparin administration in nine hemodialysis patients and controls matched for age and gender. Blood samples were drawn before heparin administration and at 15, 30, 60, 120, 180 and 240 min. RESULTS: LPL activity peaked at 15 or 30 min and then decreased to a plateau that was only 20%, of the peak. The activity was reduced in the patients by about 50% during the peak, and about 20% during the following plateau. During the peak of lipase activity the triglycerides decreased in both groups, but the change was less pronounced in patients, as was expected from the lower circulating lipase activity. During the plateau phase with low lipase activity, the triglycerides increased towards baseline values. CONCLUSIONS: During hemodialysis with heparin, there is a peak in LPL activity as well as a reduction in triglycerides during the first hour. Thereafter LPL activity decreases towards a plateau, while triglycerides increase towards baseline. The peak activity of LPL in the patients was only half that in controls, while the plateau was comparable. The data indicate that during and following each dialysis there is a period when LPL activity becomes depleted to a level that is limiting for normal lipoprotein metabolism.

  • 22.
    Näsström, Birgit
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Stegmayr, Bernd G
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap.
    Lower plasma levels of lipoprotein lipase after infusion of low molecular weight heparin than after administration of conventional heparin indicate more rapid catabolism of the enzyme2003Inngår i: Journal of Laboratory and Clinical Medicine, ISSN 1931-5244, E-ISSN 1878-1810, Vol. 142, nr 2, s. 90-99Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The functional pool of lipoprotein lipase (LPL) is anchored to heparan sulfate at the vascular endothelium. Injection of heparin releases the enzyme into the circulating blood. Animal experiments have shown that the enzyme is then extracted and degraded by the liver. Low molecular weight (LMW) heparin preparations are widely used in the clinic and are supposed to release less LPL. In this study, we infused a LMW heparin into healthy volunteers for 8 hours. The peak of LPL activity was only about 30% and the subsequent plateau of LPL activity only about 40% compared with those seen with conventional heparin. When a bolus of heparin was given after 4 hours' infusion of LMW or conventional heparin, only relatively small, and similar, amounts of LPL entered plasma. This suggests that the difference between LMW and conventional heparin lay in the ability to retain LPL in the circulating blood, not in the ability to release the lipase. Triglycerides (TGs) decreased when the heparin infusion was started, as expected from the high circulating LPL activities. After 1 to 2 hours, TG levels increased again, and after 8 hours they were about twice as high as before the heparin infusion. This indicates that the amount of LPL available for lipoprotein metabolism had become critically low in relation to TG transport rates. This study indicates that LMW heparin compared with conventional heparin causes as much or more depletion of LPL and subsequent impairment of TG clearing.

  • 23.
    Näsström, Birgit
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Gupta, Jitendra
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    A single bolus of a low molecular weight heparin to patients on haemodialysis depletes lipoprotein lipase stores and retards triglyceride clearing.2005Inngår i: Nephrology, Dialysis and Transplantation, ISSN 0931-0509, E-ISSN 1460-2385, Vol. 20, nr 6, s. 1172-1179Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Low molecular weight heparins (LMWH) are increasingly used during haemodialysis (HD) to prevent clotting in the extracorporeal devices. It has been suggested that LMWH release endothelial-bound lipoprotein lipase (LPL) less efficiently than unfractionated heparin (UFH) does and thereby cause less disturbance of lipid metabolism. Evidence from in vitro studies and from animal experiments indicate, however, that both types of heparin preparations have the same ability to release endothelial LPL, but LMWH are less effective in preventing uptake and degradation of LPL in the liver. Model studies in humans indicate that LMWH cause as much depletion of LPL stores and impaired lipolysis of triglyceride (TG)-rich lipoproteins as UFH does. METHODS: Two anticoagulant regimes based on present clinical practice were compared in nine HD patients. UFH was administered as a primed infusion, whereas the LMWH (dalteparin) was given only as a single bolus pre-dialysis. Blood was sampled regularly for LPL activity and TG. RESULTS: LPL activity in blood was significantly lower during the dialysis with dalteparin. To explore the remaining activity at the endothelium, a bolus of UFH was given after 3 h of dialysis. The bolus brought out about the same amount of LPL, regardless of whether UFH or dalteparin had been used during dialysis. The increase in TG was significantly higher during dialysis with dalteparin. CONCLUSIONS: This study indicates that a single bolus of dalteparin pre-dialysis interferes with the LPL system as much as, or more than an infusion of UFH does.

  • 24.
    Näsström, Birgit
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Stegmayr, Bernd
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Lipoprotein lipase in hemodialysis patients: indications that low molecular weight heparin depletes functional stores, despite low plasma levels of the enzyme.2004Inngår i: BMC Nephrology, ISSN 1471-2369, E-ISSN 1471-2369, Vol. 5, nr 1, s. 17-Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    BACKGROUND: Lipoprotein lipase (LPL) has a central role in the catabolism of triglyceride-rich lipoproteins. The enzyme is anchored to the vascular endothelium through interaction with heparan sulphate proteoglycans and is displaced from this interaction by heparin. When heparin is infused, there is a peak of LPL activity accompanied by a reduction in triglycerides (TG) during the first hour, followed by a decrease in LPL activity to a stable plateau during the remaining session while TG increase towards and beyond baseline. This suggests that tissue stores of LPL become depleted. It has been argued that low molecular weight (LMW) heparins cause less disturbance of the LPL system than conventional heparin does. METHODS: We have followed LPL activity and TG during a dialysis-session with a LMW heparin (dalteparin) using the same patients and regime as in a previous study with conventional heparin, i.e. a primed infusion. RESULTS: The shape of the curve for LPL activity resembled that during the earlier dialyses with conventional heparin, but the values were lower during dialysis with dalteparin. The area under the curve for LPL activity during the peak period (0-180 minutes) was only 27% and for the plateau period (180-240 minutes) it was only 36% of that observed with conventional heparin (p < 0.01). These remarkably low plasma LPL activities prompted us to re-analyze LPL activity and to measure LPL mass in frozen samples from our earlier studies. There was excellent correlation between the new and old values which rules out the possibility of assay variations as a confounding factor. TG increased from 2.14 mmol/L before, to 2.59 mmol/L after the dialysis (p < 0.01). From 30 minutes on, the TG values were significantly higher after dalteparin compared to conventional heparin (p < 0.05). CONCLUSION: These results indicate that LMW heparins disturb the LPL system as much or more than conventional heparin does.

  • 25.
    Olivecrona, Gunilla
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Ehrenborg, Ewa
    Semb, Henrik
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Makoveichuk, Elena
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Lindberg, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hayden, Michael R
    Gin, Peter
    Davies, Brandon S J
    Weinstein, Michael M
    Fong, Loren G
    Beigneux, Anne P
    Young, Stephen G
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hernell, Olle
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Mutation of conserved cysteines in the Ly6 domain of GPIHBP1 in familial chylomicronemia2010Inngår i: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 51, nr 6, s. 1535-1545Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    We investigated a family from northern Sweden in which three of four siblings have congenital chylomicronemia. Lipoprotein lipase (LPL) activity and mass in pre- and post-heparin plasma were low, and LPL release into plasma after heparin injection was delayed. LPL activity and mass in adipose tissue biopsies appeared normal. [35S]Methionine incorporation studies on adipose tissue showed that newly synthesized LPL was normal in size and normally glycosylated. Breast milk from the affected female subjects contained normal to elevated LPL mass and activity levels. The milk had a lower than normal milk lipid content, and the fatty acid composition was compatible with the milk lipids being derived from de novo lipogenesis, rather than from the plasma lipoproteins. Given the delayed release of LPL into the plasma after heparin, we suspected that the chylomicronemia might be caused by mutations in GPIHBP1. Indeed, all three affected siblings were compound heterozygotes for missense mutations involving highly conserved cysteines in the Ly6 domain of GPIHBP1 (C65S and C68G). The mutant GPIHBP1 proteins reached the surface of transfected CHO cells but were defective in their ability to bind LPL (as judged by both cell-based and cell-free LPL binding assays). Thus, the conserved cysteines in the Ly6 domain are crucial for GPIHBP1 function.

  • 26.
    Olivecrona, Gunilla
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Triglyceride lipases and atherosclerosis2010Inngår i: Current Opinion in Lipidology, ISSN 0957-9672, E-ISSN 1473-6535, Vol. 21, nr 5, s. 409-415Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    There are several ways by which derangement of the lipases may contribute to atherogenesis. Lipase actions are major determinants of plasma lipoprotein patterns. LPL activity must be modulated in relation to the physiological situation (feeding, fasting, exercise, etc.). Fatty acids and monoglycerides generated must be efficiently removed so that they do not endanger the integrity of the endothelium, cause lipotoxic reactions or both. In addition, the lipases may cause binding and endocytosis of lipoprotein particles in the artery wall.

  • 27.
    Olivecrona, T
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Bengtsson-Olivecrona, G
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hultin, M
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Peterson, J
    Vilaró, S
    Deckelbaum, R J
    Carpentier, Y A
    Patsch, J
    What factors regulate the action of lipoprotein lipase?1991Inngår i: Advances in Experimental Medicine and Biology, ISSN 0065-2598, E-ISSN 2214-8019, Vol. 285, s. 335-9Artikkel i tidsskrift (Fagfellevurdert)
  • 28.
    Olivecrona, T
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Bengtsson-Olivecrona, G
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Ostergaard, P
    Liu, G
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Chevreuil, O
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hultin, M
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    New aspects on heparin and lipoprotein metabolism.1993Inngår i: Haemostasis, ISSN 0301-0147, E-ISSN 1423-0038, Vol. 23 Suppl 1, s. 150-60Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lipoprotein lipase (LPL) and hepatic lipase (HL) are two enzymes which participate in metabolism of plasma lipoproteins. The enzymes are located at vascular surfaces and are released from their binding sites on injection of heparin. In this paper we give a short overview of the structure of the lipases and their role in lipoprotein metabolism. Earlier studies had shown that low molecular weight (LMW) heparin preparations result in lower LPL activities in blood than do corresponding amounts of conventional heparin. Studies with organ perfusion in rats show that the two types of heparin have similar ability to release the lipases from their binding sites in extrahepatic tissues, but that LMW heparin is less effective than conventional heparin in preventing rapid uptake and degradation of LPL by the liver. After injection of heparin the metabolism of triglyceride-rich lipoproteins is initially accelerated, presumably as a result of the high levels of circulating LPL. Then follows a phase when lipoprotein metabolism is slower than normal, perhaps because endothelial LPL has been depleted by accelerated transport to and degradation in the liver.

  • 29.
    Olivecrona, T
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Bergö, M
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hultin, M
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, G
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Nutritional regulation of lipoprotein lipase.1995Inngår i: Canadian Journal of Cardiology, ISSN 0828-282X, E-ISSN 1916-7075, Vol. 11 Suppl G, s. 73G-78GArtikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Lipoprotein lipase (LPL) is needed for normal catabolism of triglyceride-rich lipoproteins. In some tissues, notably the adipose tissue, the local LPL activity is an important determinant for how much lipid is taken up. There is regulation of gene expression, but the rapid changes that occur in response to the nutritional state are mediated mainly by post-transcriptional mechanisms. In the fed state, the adipose tissue expresses its full potential for LPL production, as set by the mRNA levels and the rate of protein synthesis. During fasting, LPL activity is suppressed by an unknown post-translational mechanism. In heart, regulation is primarily exerted on the equilibrium between LPL at endothelial sites and LPL in blood, with more endothelial LPL in the fasted state. LPL forms complexes with fatty acids which results in shut-down of lipolysis and detachment of both lipase and lipoproteins from the endothelial site. This provides a molecular coupling device between the cellular metabolic state and the rate of lipoprotein catabolism. There is growing evidence that LPL is a ligand for binding of lipoprotein particles such as chylomicron remnants to cell surfaces and receptors.

  • 30.
    Olivecrona, T
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hultin, M
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Bergö, M
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, G
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Lipoprotein lipase: regulation and role in lipoprotein metabolism.1997Inngår i: Proceedings of the Nutrition Society, ISSN 0029-6651, E-ISSN 1475-2719, Vol. 56, nr 2, s. 723-9Artikkel i tidsskrift (Fagfellevurdert)
  • 31.
    Olivecrona, Thomas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Liu, Guoqing
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hultin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Bengtsson-Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Regulation of lipoprotein lipase1993Inngår i: Biochemical Society Transactions, ISSN 0300-5127, E-ISSN 1470-8752, Vol. 21, nr 2, s. 509-513Artikkel i tidsskrift (Fagfellevurdert)
  • 32.
    Olivecrona, Thomas
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    The Ins and Outs of Adipose Tissue2009Inngår i: Cellular Lipid Metabolism / [ed] Christian Enholm, New York: Springer Berlin/Heidelberg, 2009, s. 315-369Kapittel i bok, del av antologi (Annet vitenskapelig)
    Abstract [en]

    The aim of this chapter is to discuss what mechanisms are available to rapidly modulate fatty acid uptake/mobilization in adipose tissue. The major pathway for net uptake is lipoprotein lipase (LPL)-mediated hydrolysis of lipoprotein lipids. There are several mechanisms for control and they all serve to suppress LPL activity on a time-scale of hours in the setting of essentially unchanged LPL mRNA and mass. A protein complex that specifically binds to LPL mRNA can block synthesis of new enzyme. The Ca2+ milieu, and perhaps other conditions in the ER, can partition more of the enzyme towards intracellular degradation and less for export. After secretion from the adipocytes, active LPL can be converted into inactive monomers through interaction with angiopoietin-like proteins. At the vascular endothelium, product control may balance LPL action. If fatty acids accumulate at sites of lipolysis they eliminate the effect of apolipoprotein CII, which is a necessary activator for LPL. Intracellular lipolysis is initiated by adipose tissue triglyceride lipase (ATGL) which hydrolyzes triglycerides to diglycerides. These can either be re-esterified by a diacylglycerol acyl transferase (DGAT) enzyme or further hydrolyzed by hormone-sensitive lipase (HSL). The system is controlled by phosphorylation mediated by protein kinase A, and perhaps other protein kinases, as well as protein phosphatases. The prime target is perilipin, a lipid droplet protein which in its unphosphorylated form suppresses the activity of both ATGL and HSL. The two lipase systems are modulated by different mechanisms and on different time-scales. Both systems seem to operate at levels that generate an excess of fatty acids. The overriding control of how Much gets deposited in the tissue as triglyceride and how much spills over into blood as albumin-bound fatty acids (NEFA) is exerted by the rate of glyceride synthesis. Recent studies show that glycerol-3-phosphate for this is generated mainly through glyceroneogenesis from citric acid cycle intermediates.

  • 33.
    Ruge, T
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Bergö, M
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hultin, M
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, G
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, T
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Nutritional regulation of binding sites for lipoprotein lipase in rat heart.2000Inngår i: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 278, nr 2, s. E211-8Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Several laboratories have shown that when rats are fasted, the amount of lipoprotein lipase (LPL) at the vascular endothelium in heart (monitored as the amount released by heparin) increases severalfold without corresponding changes in the production of LPL. This suggests that there is a change in endothelial binding of LPL. To study this, (125)I-labeled bovine LPL was injected. The fraction that bound in the heart was more than twice as high in fasted than in fed rats, 4.3% compared with 1.9% of the injected dose. Refeeding reversed this in 5 h. When unlabeled LPL was injected before the tracer, the fraction of (125)I-LPL that bound in heart decreased, indicating that the binding was saturable. When isolated hearts were perfused at 4 degrees C with a single pass of labeled LPL, twice as much bound in hearts of fasted rats. We conclude that fasting causes a change in the vascular endothelium in heart such that its ability to bind LPL increases.

  • 34.
    Savonen, R
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Nordstoga, K
    Christophersen, B
    Lindberg, A
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Shen, Y
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hultin, M
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, T
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, G
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Chylomicron metabolism in an animal model for hyperlipoproteinemia type I.1999Inngår i: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 40, nr 7, s. 1336-46Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Mink homozygous for the mutation Pro214Leu in lipoprotein lipase (LPL) had only traces of LPL activity but amounts of LPL protein in their tissues similar to those of normal mink. In normal mink, lymph chylomicrons from rats given [3H]retinol (incorporated into retinyl esters, providing a core label) and [14C]oleic acid (incorporated mainly in triglycerides (TG)) were rapidly cleared from the circulation. In the homozygous mink, clearance was much retarded. The ratio of TG to core label in plasma did not decrease and much less [14C]oleic acid appeared in plasma. Still, half of the labeled material disappeared from the circulating blood within 30;-40 min and the calculated total turnover of TG in the hypertriglyceridemic mink was almost as large as in normal mink. The core label was distributed to the same tissues in hypertriglyceridemic mink as in normal mink. Half to two-thirds of the cleared core label was in the liver. The large difference was that in the hypertriglyceridemic mink, TG label (about 40% of the total amount removed) followed the core label to the liver and there was no preferential uptake of TG over core label in adipose or muscle tissue. In normal mink, only small amounts of TG label (<10%) appeared in the liver, while most was in adipose and muscle tissues. Apolipoprotein B-48 dominated in the accumulated TG-rich lipoproteins in blood of hypertriglyceridemic mink, even in fasted animals.

  • 35.
    Savonen, Roger
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Hiden, Michaela
    Hultin, Magnus
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Zechner, Rudolf
    Levak-Frank, Sanja
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    The tissue distribution of lipoprotein lipase determines where chylomicrons bind2015Inngår i: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 56, nr 3, s. 588-598Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    To determine the role of LPL for binding of lipoproteins to the vascular endothelium, and for the distribution of lipids from lipoproteins, four lines of induced mutant mice were used. Rat chylomicrons labeled in vivo with [C-14] oleic acid (primarily in TGs, providing a tracer for lipolysis) and [H-3]retinol (primarily in ester form, providing a tracer for the core lipids) were injected. TG label was cleared more rapidly than core label. There were no differences between the mouse lines in the rate at which core label was cleared. Two minutes after injection, about 5% of the core label, and hence chylomicron particles, were in the heart of WT mice. In mice that expressed LPL only in skeletal muscle, and had much reduced levels of LPL in the heart, binding of chylomicrons was reduced to 1%, whereas in mice that expressed LPL only in the heart, the binding was increased to over 10%. The same patterns of distribution were evident at 20 min when most of the label had been cleared. Thus, the amount of LPL expressed in muscle and heart governed both the binding of chylomicron particles and the assimilation of chylomicron lipids in the tissue.

  • 36.
    Stegmayr, Bernd
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Olivecrona, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Olivecrona, Gunilla
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Fysiologisk kemi.
    Lipoprotein lipase disturbances induced by uremia and hemodialysis2009Inngår i: Seminars in dialysis, ISSN 0894-0959, E-ISSN 1525-139X, Vol. 22, nr 4, s. 442-444Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Factors such as malnutrition, physical inactivity, uremic toxins, and inflammation are known to influence the activity of lipoprotein lipase (LPL), an important enzyme in metabolism of blood lipids. In patients with chronic kidney disease these factors are common and may result in a decreased LPL activity. This is particularly so in patients on hemodialysis. Further, during each dialysis treatment, the use of heparin (or low molecular weight heparin) induces a release of LPL from its normal binding sites at the plasma membrane of endothelial cells. This results in an increased degradation of the enzyme and a relative lack of LPL activity for up to 10 hours from the start of the dialysis. Thus, the use of conventional anticoagulation for hemodialysis, in addition to the consequences of the uremic state, may cause a severe functional deficiency of LPL. This in turn may have deleterious effects on energy metabolism and may contribute to the increased risk for cardiovascular disease in this vulnerable group of patients.

1 - 36 of 36
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