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T Olivecrona

Publications and source records attributed to T Olivecrona.

At least 19 recordsLinked to original sources
PubMed2006

Pancreatitis associated with hyperlipoproteinaemia type I in mink (Mustela vison): earliest detectable changes occur in mitochondria of exocrine cells.

Pancreatic tissue from young mink homozygous for a mutation in the lipoprotein lipase gene was studied by light and electron microscopy, with the aim of describing the earliest detectable changes in a process which rapidly progresses into overt pancreatitis. The mutation leads to hyperlipoproteinaemia, corresponding to hyperlipoproteinaemia type I in man. Assessment of relevant hepatic and pancreatic enzymes were included in the investigation. The earliest detectable changes consisted of widespread swelling and vacuolation of exocrine cells, arising mainly from swollen mitochondria. To a lesser extent, vesiculation of endoplasmic reticulum occurred. Mitochondria exhibited various changes, including cavitation and dilution of the matrix, with shortened and disorganized cristae displaced towards the periphery. Lamellar figures that developed within mitochondria were numerous. Acinar lumina were somewhat dilated, while plasma membranes were relatively well preserved and secretory granules seemed unchanged. Exfoliative processes progressively occurred, resulting in total necrosis of groups of parenchymal cells, while intercalated ducts were spared. The necrosis was rapidly followed by inflammatory reactions. The activity of the mitochondrial enzyme carnitine O-palmitoyltransferase, essential for the transport of fatty acids into the mitochondria, was lower in the pancreas than in the liver. The activity of the peroxisomal fatty acid beta-oxidation was high in the liver and low in the pancreas of both lipoprotein lipase-deficient and control mink. It is concluded that pancreatic lesions associated with hyperlipoproteinaemia start in exocrine cells, and are most probably the result of a metabolic disturbance, possibly a toxic effect of an excess of free fatty acids.

Animals↗
PubMed2005

Influence of trauma on plasma elimination of exogenous fat and on lipoprotein lipase activity and mass.

BACKGROUND: Trauma is followed by an increased plasma clearance and oxidation of exogenous fat but the underlying mechanism is not fully understood. AIM: To examine the influence of a surgical trauma on the plasma elimination of exogenous triglycerides (TG) and its relationship with lipoprotein lipase (LPL) activity and LPL mass. METHODS: Nine patients underwent a hypertriglyceridaemic clamp and a lipolytic capacity test before and after open abdominal surgery. The infusion rate was adjusted to maintain a stable TG concentration of 4 mmol x l(-1) during 180 min. The lipolytic capacity was determined as the change in LPL activity and mass following a bolus dose of 100 IU x kg BW(-1) heparin sodium. RESULTS: Postoperatively, the plasma elimination rate of fat was 2.6 times higher (P<0.001). Infusion of lipids in the postoperative state was followed by a smaller rise in free fatty acids (P<0.05) in comparison with the preoperative situation. The postoperative basal fasting LPL activity was half of that in the preoperative state and the LPL activity rose almost two-fold during the clamp. The heparin-induced rises in LPL activity and LPL mass were similar (n.s.) before and after surgery. CONCLUSIONS: A moderate surgical trauma is accompanied by a greater than two-fold rise in plasma elimination rate of exogenous fat despite a lower basal LPL activity and a virtually unchanged LPL pattern during infusion of lipids. Our study demonstrates that although trauma may substantially enhance the fat elimination capacity a significant proportion of the infused fat is not utilized for metabolic purposes.

Abdomen↗
PubMed2004

Release of endothelium-associated proteins into blood by injection of heparin in normal subjects and in patients with Type 1 diabetes.

AIMS: Disturbances in heparan sulphate proteoglycans in patients with diabetic nephropathy might contribute to the pathogenesis of vascular disease in these patients. To investigate this possible link, we measured the heparin-induced, immediate release of eight proteins with heparan sulphate binding properties in patients with nephropathy. METHODS: We studied three groups, Type 1 diabetic patients with (n = 10) or without (n = 15) albuminuria and matched controls (n = 12). Blood samples were obtained before and 5 min after the injection of 40 anti-Xa IU low molecular weight heparin/kg body weight. RESULTS: Lipoprotein lipase increased more in diabetic patients without albuminuria than in controls and patients with albuminuria [261 (170-293) vs. 177 (103-438), P < 0.05 and 203 (159-280) mU/ml, P < 0.05]. Total tissue factor pathway inhibitor increased more in the diabetic patients [284 (198-449) and 275 (243-399)] than in the controls [221 (169-289) ng/ml, P < 0.005]. Vitronectin increased significantly only in the diabetic patients with albuminuria. The remaining proteins did not increase significantly (antithrombin, von Willebrand factor, fibronectin) or increased equally in the three investigated groups (extracellular superoxid dismutase and platelet factor 4). CONCLUSIONS: The different release of lipoprotein lipase and vitronectin in diabetic subjects with and without albuminuria may reflect novel aspects of vascular derangement in patients with albuminuria.

Adult↗
PubMed2003

Lipoprotein lipase during heparin infusion: lower activity in hemodialysis patients.

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.

Aged↗
PubMed2001

Food deprivation increases post-heparin lipoprotein lipase activity in humans.

OBJECTIVE: To study the effect of fasting on lipoprotein lipase (LPL) activity in human post-heparin plasma, representing the functional pool of LPL. DESIGN: Fourteen healthy volunteers were recruited for the study. The subjects were fasted for 30 h. Activities of LPL and hepatic lipase (HL), and LPL mass, were measured in pre- and post-heparin plasma in the fed and in the fasted states, respectively. For comparison, LPL and HL activities were measured in pre- and post-heparin plasma from fed and 24-h-fasted guinea pigs. RESULTS: Fasting caused a significant drop in the levels of serum insulin, triglycerides and glucose in the human subjects. Post-heparin LPL activity increased from 79 +/- 6.4 mU mL-1 in the fed state to 112 +/- 10 mU mL-1 in the fasted state (P < 0.01), while LPL mass was 361 +/- 29 in the fed state and 383 +/- 28 in the fasted state, respectively (P = 0.6). In contrast, fasting of guinea pigs caused an 80% drop in post-heparin LPL activity. The effect of fasting on human and guinea pig post-heparin HL activity were moderate and statistically not significant. CONCLUSIONS: In animal models such as rats and guinea pigs, post-heparin LPL activity decreases on fasting, presumably due to down-regulation of adipose tissue LPL. In humans, fasting caused increased post-heparin LPL activity.

Adipose Tissue↗
PubMed2001

Lipoprotein lipase during continuous heparin infusion: tissue stores become partially depleted.

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.

Aged↗
PubMed2000

Nutritional regulation of binding sites for lipoprotein lipase in rat heart.

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.

Adipose Tissue↗
PubMed1999

Chylomicron metabolism in an animal model for hyperlipoproteinemia type I.

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.

Amino Acid Substitution↗
PubMed1998

Effect of the calcium channel antagonist nitrendipine on lipoprotein lipase and hepatic lipase in the normal rat.

Several observations indicate that a low lipoprotein lipase (LPL)/hepatic lipase (HL) ratio clusters with clinical and laboratory features of atherosclerosis. Antihypertensive treatment can unfavourably interfere with lipid metabolism, counteracting the beneficial effects of lowering blood pressure. We have evaluated the effects of the Ca2+ channel antagonist nitrendipine on tissue LPL and HL in the normal rat. At the dose of 40 mg/day administered intragastrically, a 5-day nitrendipine treatment induced a significant decrease in HL activity in the liver, in comparison to control animals: 656 +/-82 mU/g tissue vs. 814+/-38 mU/g 3 h after the last administration; 640+/-70 mU/g vs. 893+/-101 mU/g 8 h after administration. LPL activity in heart was increased by active treatment: 2542+/-298 vs. 2115+/-244 mU/g in controls 3 h after administration, P < 0.05. At variance, LPL mass, measured 8 h after administration, was decreased in heart of treated rats: 2.38+/-0.4 microg/g tissue vs. 3.88+/-0.3 microg/g in controls. The ratio between heparin-releasable and residual LPL in heart was unaffected by the drug. No changes were observed in LPL activity and mass in soleus muscle or in periepididymal adipose tissue. Our results indicate that nitrendipine, at the dose used, induces changes in lipolytic enzymes of rat tissues that could be beneficial in relation to atherosclerosis. These data encourage further investigations in humans, at the usual therapeutical doses.

Adipose Tissue↗
PubMed1998

Conversion of chylomicrons into remnants.

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.

Animals↗
PubMed1998

Lipoprotein lipase activity and mRNA levels in bovine tissues.

Lipoprotein lipase (LPL) in cattle has been extensively studied in adipose tissue, milk and mammary gland, but only to a limited extent in muscles. Therefore, we have adapted our in vitro LPL assay method for the measurement of LPL activity and describe, for the first time, sensitive procedures to quantify LPL activity and mRNA levels in bovine muscles. In vitro activation of bovine LPL activity is approximately 5-fold greater with rat than with bovine sera for heart and muscles, but not for adipose tissues. Values of LPL activity are in the upper range of those previously reported for rat or bovine tissues. With rat serum as activator, LPL activity in the heart of seven calves (662-832 mU g-1) is at least 3-fold lower than in the rat heart (2150-2950 mU g-1, P < 0.05). LPL activity is higher in bovine heart and oxidative muscles (412-972 mU g-1), except the diaphragm, than in mixed or glycolytic muscles (33-154 mU g-1, P < 0.05). The levels of LPL transcripts are positively related to LPL activity in bovine tissues, including muscles and adipose tissues.

Adipose Tissue↗
PubMed1998

Clearance of artificial triacylglycerol particles.

In this review we discuss the metabolism of parenteral emulsions in relation to their natural counterpart, the chylomicrons. A major reaction is lipoprotein lipase-mediated hydrolysis of triglycerides at the vascular endothelium in extrahepatic tissues. The lipase is retained at the cell surface by interactions with heparan sulfate proteoglycans but can move along the surface. Lipoproteins and emulsion particles are initially steered to the endothelium by electrostatic forces. These weak interactions are reinforced by recruitment of lipase molecules. Small particles, whether injected as such or formed as remnants of larger particles, are catabolized mainly through receptor-mediated endocytosis in the liver. In contrast, many of the larger particles are removed by other, less well defined, mechanisms.

Animals↗
PubMed1998

Lipoprotein lipase transport in plasma: role of muscle and adipose tissues in regulation of plasma lipoprotein lipase concentrations.

Lipoprotein lipase (LPL) is synthesized in tissues involved in fatty acid metabolism such as muscle and adipose tissue. LPL is also found in the circulation, but is mostly lipolytically inactive. The proportion of active circulating LPL increases after a fatty meal. We investigated the release of active and inactive LPL from adipose tissue and muscle in the fasting and postprandial states. Arteriovenous concentration gradients of LPL across adipose tissue and forearm muscle were measured in male subjects before and after a fat-rich meal (n = 7) and before and during infusion of a triacylglycerol emulsion (Intralipid) (n = 6). Plasma LPL activity rose after the meal and more so during Intralipid infusion. Plasma LPL mass (>95% inactive LPL) increased after the meal but decreased after Intralipid infusion. In the fasting state (n = 13) muscle efflux of LPL activity was 0.263 +/- 0.098 mU/min per 100 ml of muscle tissue whereas there was an influx of LPL activity to adipose tissue of 0.085 +/- 0.100 mU/min per 100 g of adipose tissue (P < 0. 02 muscle vs. adipose tissue). Similarly in the postprandial state only muscle released LPL activity. Both tissues released LPL mass. In the fasting state efflux was 17.8 +/- 8.8 ng/min per 100 ml muscle and 55.2 +/- 21.3 ng/min per 100 g of adipose tissue (P < 0. 05 muscle vs. adipose tissue). Release of LPL, either active or inactive, was not correlated with levels of non-esterified fatty acids or plasma triacylglycerol. In conclusion, there is a substantial release of LPL from adipose tissue and muscle, most of which is inactive. A small proportion of active LPL seems to be redistributed from muscle to adipose tissue.

Adipose Tissue↗
PubMed1997

Regulation of adipose tissue lipoprotein lipase in young and old rats.

OBJECTIVE: Changes in tissue lipoprotein lipase have been reported in several of the metabolic disorders commonly associated with ageing, like insulin resistance, obesity and impaired hormonal balance. We have investigated the effect of normal ageing on the nutritional regulation of lipoprotein lipase (LPL) in rat tissues. MEASUREMENTS: In the first experiment, LPL activity and immunoreactive mass were measured in epididymal and perirenal adipose tissue, and soleus and heart muscle tissue. In the following experiments we focused on epididymal adipose tissue. RESULTS: In young rats (aged 29 d, 87 +/- 5 g), fasting for 24 h decreased LPL activity in epididymal and perirenal adipose tissue to 31% and 51% of fed control, respectively, while LPL mass increased to 146% and 261%, respectively. Consequently, LPL specific activity (activity/mass ratio) decreased to 20% of control. Other tissues studied did not show any large changes in LPL specific activity with the nutritional state. This suggests that the mechanism responsible for the down-regulation of LPL specific activity is specific for adipose tissue. The down-regulation was gradually blunted with increasing age and was non-existent in the old rats (aged 265 d, 564 +/- 14 g). LPL in soleus muscle from young rats was regulated by another mechanism, and was associated with a large increase in LPL activity and mass during fasting (297% and 458% of fed control). Also, this mechanism did not exist in soleus muscle from old rats. Prolonging the fasting period of the old rats to 96 h did not induce the changes in adipose tissue or soleus muscle LPL seen in the young rats. CONCLUSION: The results indicate that the nutritional regulation of LPL in adipose tissue and soleus muscle changes during normal ageing.

Adipose Tissue↗
PubMed1997

Lipoprotein lipase deficiency with pancreatitis in mink: biochemical characterization and pathology.

A severe hyperlipemia in mink, with a pattern that suggested recessive inheritance, was observed at a farm in Norway. On a normal mink diet, affected animals had grossly elevated levels of plasma triglycerides which decreased towards normal on a low-fat diet. Normal minks had the main part of their plasma cholesterol in the HDL fraction. Affected minks, although severely hypertriglyceridaemic, had almost normal levels of both LDL and HDL. Affected minks frequently had lipogranulomas in the mesentery and the pancreas. The lipogranulomatous tissue contained spaces filled with an amorphous, sudanophilic substance with many foamy macrophages in the fibrous tissue between the lesions. Separation of postheparin plasma on heparin-agarose revealed that the affected minks had no detectable lipoprotein lipase activity but normal activity of hepatic lipase. Both normal and affected minks had inactive lipoprotein lipase protein in pre- and post-heparin plasma. This protein, which eluted before the active lipase from heparin-agarose, probably corresponds to lipase monomers. The presence of lipoprotein lipase mass in the affected minks, but no activity, indicates that there might be a point mutation in the lipase gene. The minks provide a new animal model for studies on pancreatitis induced by hypertriglyceridemia and on lipoprotein metabolism in the lipoprotein lipase-deficient state and show features similar to those found in human hyperlipoproteinemia type I.

Animals↗
PubMed1997

Chylomicron/chylomicron remnant turnover in humans: evidence for margination of chylomicrons and poor conversion of larger to smaller chylomicron remnants.

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.

Adolescent↗
PubMed1996

Heparin-decasaccharides impair the catabolism of chylomicrons.

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.

Animals↗