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Lipoprotein lipase enhances removal of chylomicrons and chylomicron remnants by the perfused rat liver.
J Lipid Res. 1995 Jun; 36(6):1334-44.JL

Abstract

Lipoprotein lipase has been found to efficiently mediate binding of lipoproteins to cell surfaces and to the low density lipoprotein (LDL) receptor-related protein (LRP) under cell culture conditions (Beisiegel et al. 1991. Proc. Natl. Acad. Sci. USA. 88: 8242-8346). This supports the previously proposed idea that the lipase could have a role in receptor-mediated uptake of chylomicron remnants in the liver. We have investigated the effects of lipoprotein lipase on the clearance of chylomicrons during perfusions of rat livers. The chylomicrons were doubly labeled in vivo with [14C]retinol (in retinyl esters) and with [3H]oleic acid (in triacylglycerols) and were collected from lymph. In the absence of any lipase the clearance of chylomicron label from the perfusion medium was slow. Addition of lipoprotein lipase caused lipolysis of chylomicron triacylglycerols as evidenced by increased levels of 14C-labeled fatty acids in the perfusate. Simultaneously, the level of [14C]retinyl esters in the perfusate decreased dramatically, indicating core-particle removal. Similar effects were seen with an unrelated lipase from Pseudomonas fluorescens. To discriminate between the effects of lipolysis and a true liganding effect of the lipoprotein lipase protein, the active site inhibitors tetrahydrolipstatinR and hexadecylsulfonylfluoride were used to reduce or totally inhibit the catalytical activity. With lipase covalently inhibited by the latter inhibitor, lipolysis during perfusions was low or absent. Nonetheless, the inhibited enzyme had a clear effect on the removal of chylomicrons by the liver. With 1.2 micrograms of inhibited lipase/ml perfusate, about 70% of the core label had been removed after 15 min as compared to about 20% in perfusions without lipase. With identical amounts of active lipoprotein lipase protein, more than 90% of the label was removed. We conclude that any lipase causing lipolysis of chylomicrons can stimulate their clearance by the liver, but that lipoprotein lipase has an additional effect on the removal, which is not dependent on its catalytic activity.

Authors+Show Affiliations

Department of Medical Biochemistry and Biophysics, Umeå University, Sweden.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

7666010

Citation

Skottova, N, et al. "Lipoprotein Lipase Enhances Removal of Chylomicrons and Chylomicron Remnants By the Perfused Rat Liver." Journal of Lipid Research, vol. 36, no. 6, 1995, pp. 1334-44.
Skottova N, Savonen R, Lookene A, et al. Lipoprotein lipase enhances removal of chylomicrons and chylomicron remnants by the perfused rat liver. J Lipid Res. 1995;36(6):1334-44.
Skottova, N., Savonen, R., Lookene, A., Hultin, M., & Olivecrona, G. (1995). Lipoprotein lipase enhances removal of chylomicrons and chylomicron remnants by the perfused rat liver. Journal of Lipid Research, 36(6), 1334-44.
Skottova N, et al. Lipoprotein Lipase Enhances Removal of Chylomicrons and Chylomicron Remnants By the Perfused Rat Liver. J Lipid Res. 1995;36(6):1334-44. PubMed PMID: 7666010.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Lipoprotein lipase enhances removal of chylomicrons and chylomicron remnants by the perfused rat liver. AU - Skottova,N, AU - Savonen,R, AU - Lookene,A, AU - Hultin,M, AU - Olivecrona,G, PY - 1995/6/1/pubmed PY - 1995/6/1/medline PY - 1995/6/1/entrez SP - 1334 EP - 44 JF - Journal of lipid research JO - J Lipid Res VL - 36 IS - 6 N2 - Lipoprotein lipase has been found to efficiently mediate binding of lipoproteins to cell surfaces and to the low density lipoprotein (LDL) receptor-related protein (LRP) under cell culture conditions (Beisiegel et al. 1991. Proc. Natl. Acad. Sci. USA. 88: 8242-8346). This supports the previously proposed idea that the lipase could have a role in receptor-mediated uptake of chylomicron remnants in the liver. We have investigated the effects of lipoprotein lipase on the clearance of chylomicrons during perfusions of rat livers. The chylomicrons were doubly labeled in vivo with [14C]retinol (in retinyl esters) and with [3H]oleic acid (in triacylglycerols) and were collected from lymph. In the absence of any lipase the clearance of chylomicron label from the perfusion medium was slow. Addition of lipoprotein lipase caused lipolysis of chylomicron triacylglycerols as evidenced by increased levels of 14C-labeled fatty acids in the perfusate. Simultaneously, the level of [14C]retinyl esters in the perfusate decreased dramatically, indicating core-particle removal. Similar effects were seen with an unrelated lipase from Pseudomonas fluorescens. To discriminate between the effects of lipolysis and a true liganding effect of the lipoprotein lipase protein, the active site inhibitors tetrahydrolipstatinR and hexadecylsulfonylfluoride were used to reduce or totally inhibit the catalytical activity. With lipase covalently inhibited by the latter inhibitor, lipolysis during perfusions was low or absent. Nonetheless, the inhibited enzyme had a clear effect on the removal of chylomicrons by the liver. With 1.2 micrograms of inhibited lipase/ml perfusate, about 70% of the core label had been removed after 15 min as compared to about 20% in perfusions without lipase. With identical amounts of active lipoprotein lipase protein, more than 90% of the label was removed. We conclude that any lipase causing lipolysis of chylomicrons can stimulate their clearance by the liver, but that lipoprotein lipase has an additional effect on the removal, which is not dependent on its catalytic activity. SN - 0022-2275 UR - https://www.unboundmedicine.com/medline/citation/7666010/Lipoprotein_lipase_enhances_removal_of_chylomicrons_and_chylomicron_remnants_by_the_perfused_rat_liver_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0022-2275(20)41141-1 DB - PRIME DP - Unbound Medicine ER -