| 1. |
- Hultin, M, et al.
(författare)
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Metabolism of emulsions containing medium- and long-chain triglycerides or interesterified triglycerides.
- 1994
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 35:10, s. 1850-60
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Ruge, T, et al.
(författare)
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Food deprivation increases post-heparin lipoprotein lipase activity in humans.
- 2001
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Ingår i: European Journal of Clinical Investigation. - 0014-2972 .- 1365-2362. ; 31:12, s. 1040-7
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Ruge, T, et al.
(författare)
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Nutritional regulation of binding sites for lipoprotein lipase in rat heart.
- 2000
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - 0193-1849 .- 1522-1555. ; 278:2, s. E211-8
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Hultin, M, et al.
(författare)
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Effect of protamine on lipoprotein lipase and hepatic lipase in rats.
- 1994
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Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 304 ( Pt 3), s. 959-66
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Hultin, M, et al.
(författare)
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Release of lipoprotein lipase to plasma by triacylglycerol emulsions. Comparison to the effect of heparin.
- 1992
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Ingår i: Biochimica et Biophysica Acta. - 0006-3002 .- 1878-2434. ; 1125:1, s. 97-103
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 6. |
- Mohammad, M. A., et al.
(författare)
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Trends in Clinical Practice and Outcomes After Percutaneous Coronary Intervention of Unprotected Left Main Coronary Artery
- 2022
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Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- Background The use of percutaneous coronary intervention (PCI) to treat unprotected left main coronary artery disease has expanded rapidly in the past decade. We aimed to describe nationwide trends in clinical practice and outcomes after PCI for left main coronary artery disease. Methods and Results Patients (n=4085) enrolled in the SCAAR (Swedish Coronary Angiography and Angioplasty Registry) as undergoing PCI for left main coronary artery disease from 2005 to 2017 were included. A count regression model was used to analyze time-related differences in procedural characteristics. The 3-year major adverse cardiovascular and cerebrovascular event rate defined as death, myocardial infarction, stroke, and repeat revascularization was calculated with the Kaplan-Meier estimator and Cox proportional hazard model. The number of annual PCI procedures grew from 121 in 2005 to 589 in 2017 (389%). The increase was greater for men (479%) and individuals with diabetes (500%). Periprocedural complications occurred in 7.9%, decreasing from 10% to 6% during the study period. A major adverse cardiovascular and cerebrovascular event occurred in 35.7% of patients, falling from 45.6% to 23.9% (hazard ratio, 0.56; 95% CI, 0.41-0.78; P=0.001). Radial artery access rose from 21.5% to 74.2% and intracoronary diagnostic procedures from 14.0% to 53.3%. Use of bare-metal stents and first-generation drug-eluting stents fell from 19.0% and 71.9%, respectively, to 0, with use of new-generation drug-eluting stents increasing to 95.2%. Conclusions Recent changes in clinical practice relating to PCI for left main coronary artery disease are characterized by a 4-fold rise in procedures conducted, increased use of evidence-based adjunctive treatment strategies, intracoronary diagnostics, newer stents, and more favorable outcomes.
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| 7. |
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| 8. |
- Olivecrona, Henrik, et al.
(författare)
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A new CT method for measuring cup orientation after total hip arthroplasty : A study of 10 patients
- 2004
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Ingår i: Acta Orthopaedica Scandinavica. - : Medical Journals Sweden AB. - 0001-6470. ; 75:3, s. 252-260
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Tidskriftsartikel (refereegranskat)abstract
- Background It is difficult to assess the orientation of the acetabular component on routine radiographs. We present a method for determining the spatial orientation of the acetabular component after total hip arthroplasty (THA) using computed tomography. Patients and methods Two CT-scans, 10 min apart, were obtained from each of 10 patients after THA. Using locally developed software, two independent examiners measured the orientation of the acetabular component in relation to the pelvis. The measurements were repeated after one week. To be independent of the patient position during scanning, the method involved two steps. Firstly, a 3D volumetric image of the pelvis was brought into a standard pelvic orientation, then the orientation of the acetabular component was measured. The orientation of the acetabular component was expressed as operative anteversion and inclination relative to an internal pelvic reference coordinate system. To evaluate precision, we compared measurements across pairs of CT volumes between observers and trials. Results Mean absolute interobserver angle error was 2.3degrees for anteversion (range 0-6.6degrees), and 1.1degrees for inclination (range 0-4.6degrees). For interobserver measurements, the precision, defined as one standard deviation, was 2.9degrees for anteversion, and 1.5degrees for inclination. A Student's West showed that the overall differences between the examiners, trials, and cases were not significant. Data were normally distributed and were not dependent on examiner or trial. Interpretation We conclude that the implant angles of the acetabular component in relation to the pelvis could be detected repeatedly using CT, independently of patient positioning.
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| 9. |
- Olivecrona, Henrik, et al.
(författare)
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Spatial component position in total hip arthroplasty - Accuracy and repeatability with a new CT method
- 2003
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 44:1, s. 84-91
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: 3D detection of centerpoints of prosthetic cup and head after total hip arthroplasty (THA) using CT. Material and Methods: Two CT examinations, 10 min apart, were obtained from each of 10 patients after THA. Two independent examiners placed landmarks in images of the prosthetic cup and head. All landmarking was repeated after 1 week. Centerpoints were calculated and compared. Results: Within volumes, all measurements of centerpoints of cup and head fell, with a 95% confidence, within one CT-voxel of any other measurement of the same object. Across two volumes, the mean error of distance between center of cup and prosthetic head was 1.4 mm (SD 0.73). Intra- and interobserver 95% accuracy limit was below 2 mm within and below 3 mm across volumes. No difference between intra- and interobserver measurements occurred. A formula for converting finite sets of point landmarks in the radiolucent tread of the cup to a centerpoint was stable. The percent difference of the landmark distances from a calculated spherical surface was within one CT-voxel. This data was normally distributed and not dependent on observer or trial. Conclusion: The true 3D position of the centers of cup and prosthetic head can be detected using CT. Spatial relationship between the components can be analyzed visually and numerically.
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| 10. |
- Olivecrona, H, et al.
(författare)
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Stability of acetabular axis after total hip arthroplasty, repeatability using CT and a semiautomated program for volume fusion
- 2003
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Ingår i: Acta radiologica (Stockholm, Sweden : 1987). - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 44:6, s. 653-661
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To validate a CT method for detecting changes in acetabular cup orientation after THA Material and Methods: 26 CT examinations were obtained from a pelvic model with an uncemented acetabular cup. The model position was altered between acquisitions, but the cup axis angle vis-à-visthe pelvis was maintained. Data sets were combined into 37 pairs, each containing a unique positioning error. The pelvi in different examinations were fused, creating transformed volumes. Landmarks corresponding to the cup before and after fusion were placed interactively by two independent examiners. The orientation of the acetabular axis was calculated for each volume and compared across volumes. Results: Before fusion the mean angle error between the acetabular axes was 4.17° (SD ± 1.95°). After fusion the mean angle error was 0.36° (SD ± 0.17). The 95% repeatability limits were below 0.7°. There was no significant interobserver difference. Analysis of the cup landmarking pattern by condition numbers and individual landmark errors showed stability. Conclusion: Non-invasive fusion of CT volumes and a stable landmarking pattern for the acetabular cup outperforms routine plain radiography in detecting changes in the orientation of the acetabular axis over time. The method delivers both visual and numerical output and could be used in clinical practice.
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| 11. |
- Olivecrona, Henrik, et al.
(författare)
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Stability of acetabular axis after total hip arthroplasty, repeatability using CT and a semiautomated program for volume fusion
- 2003
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Ingår i: Acta Radiologica. - : SAGE Publications. - 0284-1851 .- 1600-0455. ; 44:6, s. 653-661
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To validate a CT method for detecting changes in acetabular cup orientation after THA. Material and Methods: 26 CT examinations were obtained from a pelvic model with an uncemented acetabular cup. The model position was altered between acquisitions, but the cup axis angle vis-a-vis the pelvis was maintained. Data sets were combined into 37 pairs, each containing a unique positioning error. The pelvi in different examinations were fused, creating transformed volumes. Landmarks corresponding to the cup before and after fusion were placed interactively by two independent examiners. The orientation of the acetabular axis was calculated for each volume and compared across volumes. Results: Before fusion the mean angle error between the acetabular axes was 4.17degrees (SD +/- 1.95degrees). After fusion the mean angle error was 0.36degrees (SD +/- 0.17). The 95% repeatability limits were below 0.7degrees. There was no significant interobserver difference. Analysis of the cup landmarking pattern by condition numbers and individual landmark errors showed stability. Conclusion: Non-invasive fusion of CT volumes and a stable landmarking pattern for the acetabular cup outperforms routine plain radiography in detecting changes in the orientation of the acetabular axis over time. The method delivers both visual and numerical output and could be used in clinical practice.
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| 12. |
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| 13. |
- Olivecrona, T, et al.
(författare)
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New aspects on heparin and lipoprotein metabolism.
- 1993
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Ingår i: Haemostasis. - 0301-0147 .- 1423-0038. ; 23 Suppl 1, s. 150-60
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 14. |
- Olivecrona, T, et al.
(författare)
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Nutritional regulation of lipoprotein lipase.
- 1995
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Ingår i: Canadian Journal of Cardiology. - 0828-282X .- 1916-7075. ; 11 Suppl G, s. 73G-78G
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 15. |
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| 16. |
- Savonen, R, et al.
(författare)
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Chylomicron metabolism in an animal model for hyperlipoproteinemia type I.
- 1999
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 40:7, s. 1336-46
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 17. |
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| 18. |
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| 19. |
- Blanchard, P. G., et al.
(författare)
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Peroxisome proliferator-activated receptor activation favours selective subcutaneous lipid deposition by coordinately regulating lipoprotein lipase modulators, fatty acid transporters and lipogenic enzymes
- 2016
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Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 217:3, s. 227-239
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Peroxisome proliferator-activated receptor (PPAR) γ activation is associated with preferential lipoprotein lipase (LPL)-mediated fatty acid storage in peripheral subcutaneous fat depots. How PPARγ agonism acts upon the multi-level modulation of depot-specific lipid storage remains incompletely understood.Methods: We evaluated herein triglyceride-derived lipid incorporation into adipose tissue depots, LPL mass and activity, mRNA levels and content of proteins involved in the modulation of LPL activity and fatty acid transport, and the expression/activity of enzymes defining adipose tissue lipogenic potential in rats treated with the PPARγ ligand rosiglitazone (30 mg kg−1 day−1, 23 days) after either a 10-h fasting period or a 17-h fast followed by 6 h of ad libitum refeeding.Results: Rosiglitazone stimulated lipid accretion in subcutaneous fat (SF) ~twofold and significantly reduced that of visceral fat (VF) to nearly half. PPARγ activation selectively increased LPL mass, activity and the expression of its chaperone LMF1 in SF. In VF, rosiglitazone had no effect on LPL activity and downregulated the mRNA levels of the transendothelial transporter GPIHBP1. Overexpression of lipid uptake and fatty acid transport proteins (FAT/CD36, FATP1 and FABP4) and stimulation of lipogenic enzyme activities (GPAT, AGPAT and DGAT) upon rosiglitazone treatment were of higher magnitude in SF.Conclusions: Together these findings demonstrate that the depot-specific transcriptional control of LPL induced by PPARγ activation extends to its key interacting proteins and post-translational modulators to favour subcutaneous lipid storage.
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| 20. |
- Chevreuil, O, et al.
(författare)
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Biphasic effects of low-molecular-weight and conventional heparins on chylomicron clearance in rats.
- 1993
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Ingår i: Arteriosclerosis and thrombosis : a journal of vascular biology / American Heart Association. - 1049-8834. ; 13:10, s. 1397-403
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Tidskriftsartikel (refereegranskat)abstract
- 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)
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| 21. |
- Chevreuil, O, et al.
(författare)
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Depletion of lipoprotein lipase after heparin administration.
- 1993
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Ingår i: Arteriosclerosis and thrombosis : a journal of vascular biology / American Heart Association. - 1049-8834. ; 13:10, s. 1391-6
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Tidskriftsartikel (refereegranskat)abstract
- 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)
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| 22. |
- Chevreuil, O, et al.
(författare)
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Heparin-decasaccharides impair the catabolism of chylomicrons.
- 1996
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Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 320 ( Pt 2), s. 437-44
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 23. |
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| 24. |
- Hultin, M, et al.
(författare)
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Chylomicron metabolism in rats : lipolysis, recirculation of triglyceride-derived fatty acids in plasma FFA, and fate of core lipids as analyzed by compartmental modelling.
- 1996
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 37:5, s. 1022-36
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 25. |
- Hultin, M, et al.
(författare)
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Conversion of chylomicrons into remnants.
- 1998
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Ingår i: Atherosclerosis. - 0021-9150 .- 1879-1484. ; 141 Suppl 1, s. S25-9
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 26. |
- Hultin, M, et al.
(författare)
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Intravenous lipid emulsions : removal mechanisms as compared to chylomicrons.
- 1995
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 36:10, s. 2174-84
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 27. |
- Karpe, F, et al.
(författare)
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Chylomicron/chylomicron remnant turnover in humans : evidence for margination of chylomicrons and poor conversion of larger to smaller chylomicron remnants.
- 1997
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Ingår i: Journal of Lipid Research. - 0022-2275 .- 1539-7262. ; 38:5, s. 949-61
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 28. |
- Kristensen, Kristian K., et al.
(författare)
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Unfolding of monomeric lipoprotein lipase by ANGPTL4 : Insight into the regulation of plasma triglyceride metabolism
- 2020
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 117:8, s. 4337-4346
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Tidskriftsartikel (refereegranskat)abstract
- The binding of lipoprotein lipase (LPL) to GPIHBP1 focuses the intravascular hydrolysis of triglyceride-rich lipoproteins on the surface of capillary endothelial cells. This process provides essential lipid nutrients for vital tissues (e.g., heart, skeletal muscle, and adipose tissue). Deficiencies in either LPL or GPIHBP1 impair triglyceride hydrolysis, resulting in severe hypertriglyceridemia. The activity of LPL in tissues is regulated by angiopoietin-like proteins 3, 4, and 8 (ANGPTL). Dogma has held that these ANGPTLs inactivate LPL by converting LPL homodimers into monomers, rendering them highly susceptible to spontaneous unfolding and loss of enzymatic activity. Here, we show that binding of an LPL-specific monoclonal antibody (5D2) to the tryptophan-rich lipid-binding loop in the carboxyl terminus of LPL prevents homodimer formation and forces LPL into a monomeric state. Of note, 5D2-bound LPL monomers are as stable as LPL homodimers (i.e., they are not more prone to unfolding), but they remain highly susceptible to ANGPTL4-catalyzed unfolding and inactivation. Binding of GPIHBP1 to LPL alone or to 5D2-bound LPL counteracts ANGPTL4-mediated unfolding of LPL. In conclusion, ANGPTL4-mediated inactivation of LPL, accomplished by catalyzing the unfolding of LPL, does not require the conversion of LPL homodimers into monomers. Thus, our findings necessitate changes to long-standing dogma on mechanisms for LPL inactivation by ANGPTL proteins. At the same time, our findings align well with insights into LPL function from the recent crystal structure of the LPL•GPIHBP1 complex.
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| 29. |
- Laplante, Mathieu, et al.
(författare)
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Tissue-specific postprandial clearance is the major determinant of PPARgamma-induced triglyceride lowering in the rat
- 2009
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Ingår i: American Journal of Physiology. Regulatory Integrative and Comparative Physiology. - Bethesda, Md. : American Physiological Society. - 0363-6119 .- 1522-1490. ; 296:1, s. R57-R66
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Tidskriftsartikel (refereegranskat)abstract
- Peroxisome proliferator-activated receptor-gamma (PPARgamma) agonism potently reduces circulating triglycerides (TG) in rodents and more modestly so in humans. This study aimed to quantify in vivo the relative contribution of hepatic VLDL-TG secretion and tissue-specific TG clearance to such action. Rats were fed an obesogenic diet, treated with the PPARgamma full agonist COOH (30 mg.kg(-1).day(-1)) for 3 wk, and studied in both the fasted and refed (fat-free) states. Hepatic VLDL-TG secretion rate was not affected by chronic COOH in the fasted state and was only modestly decreased (-30%) in refed rats. In contrast, postprandial VLDL-TG clearance was increased 2.6-fold by COOH, which concomitantly stimulated adipose tissue TG-derived lipid uptake and one of its major determinants, lipoprotein lipase (LPL) activity, in a highly depot-specific manner. TG-derived lipid uptake and LPL were indeed strongly increased in subcutaneous inguinal white adipose tissue and in brown adipose tissue, independently of the nutritional state, whereas of the three visceral fat depots examined (epididymal, retroperitoneal, mesenteric) only the latter responded consistently to COOH. Robust correlations (0.5 < r < 0.9) were observed between TG-derived lipid uptake and LPL in adipose tissues. The agonist did not increase LPL in muscle, and its enhancing action on postprandial muscle lipid uptake appeared to be mediated by post-LPL processes involving increased expression of fatty acid binding/transport proteins (aP2, likely in infiltrated adipocytes, FAT/CD36, and FATP-1). The study establishes in a diet-induced obesity model the major contribution of lipid uptake by specific, metabolically safe adipose depots to the postprandial hypotriglyceridemic action of PPARgamma agonism, and suggests a key role for LPL therein.
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| 30. |
- Liu, G, et al.
(författare)
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Interaction of size-fractionated heparins with lipoprotein lipase and hepatic lipase in the rat.
- 1992
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Ingår i: Biochemical Journal. - 0264-6021 .- 1470-8728. ; 285 ( Pt 3), s. 731-6
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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