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. 1996 Feb 1;313(Pt 3):893–898. doi: 10.1042/bj3130893

Forms of lipoprotein lipase in rat tissues: in adipose tissue the proportion of inactive lipase increases on fasting.

M Bergö 1, G Olivecrona 1, T Olivecrona 1
PMCID: PMC1216995  PMID: 8611172

Abstract

Previous studies have shown that the ratio of lipoprotein lipase (LPL) catalytic activity to LPL mass in tissues differs in different conditions, but it is not clear whether this occurs by a change in the catalytic efficiency of the LPL molecules, or because of a shift in the relation between active and inactive forms of the enzyme. To explore this, we have measured LPL activity and mass in detergent extracts of rat tissues. LPL specific activity was high and similar in heart, skeletal muscle, lung and brain. The liver had significantly lower specific activity, which is in accord with previous findings that the liver takes up and catabolizes LPL. The specific activity was also low in adipose tissue from fasted rats. When tissue extracts were applied to columns of heparin-agarose and eluted by a gradient of NaCl, a peak of active LPL was eluted at 1.0 M NaCl, but there was also a peak of inactive LPL protein, which was eluted at 0.6 M NaCl. In adipose tissue, LPL activity decreased by 70-80% during an overnight fast, whereas LPL mass decreased by only 20-40%. The mass ratio between inactive and active LPL, as separated by heparin-agarose chromatography, increased from 0.5 to over 2 during the fast. In hearts there was no significant difference between fed and fasted rats in total LPL activity, LPL mass or in the distribution between inactive and active forms. The results indicate that the relation between inactive (probably monomeric) and active (dimeric) forms of LPL is a target for post-translational regulation in adipose tissue.

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Selected References

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  1. Amri E. Z., Vannier C., Etienne J., Ailhaud G. Maturation and secretion of lipoprotein lipase in cultured adipose cells. II. Effects of tunicamycin on activation and secretion of the enzyme. Biochim Biophys Acta. 1986 Feb 12;875(2):334–343. doi: 10.1016/0005-2760(86)90184-0. [DOI] [PubMed] [Google Scholar]
  2. Ashby P., Bennett D. P., Spencer I. M., Robinson D. S. Post-translational regulation of lipoprotein lipase activity in adipose tissue. Biochem J. 1978 Dec 15;176(3):865–872. doi: 10.1042/bj1760865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ben-Zeev O., Doolittle M. H., Davis R. C., Elovson J., Schotz M. C. Maturation of lipoprotein lipase. Expression of full catalytic activity requires glucose trimming but not translocation to the cis-Golgi compartment. J Biol Chem. 1992 Mar 25;267(9):6219–6227. [PubMed] [Google Scholar]
  4. Ben-Zeev O., Doolittle M. H., Singh N., Chang C. H., Schotz M. C. Synthesis and regulation of lipoprotein lipase in the hippocampus. J Lipid Res. 1990 Jul;31(7):1307–1313. [PubMed] [Google Scholar]
  5. Ben-Zeev O., Lusis A. J., LeBoeuf R. C., Nikazy J., Schotz M. C. Evidence for independent genetic regulation of heart and adipose lipoprotein lipase activity. J Biol Chem. 1983 Nov 25;258(22):13632–13636. [PubMed] [Google Scholar]
  6. Bengtsson-Olivecrona G., Olivecrona T. Binding of active and inactive forms of lipoprotein lipase to heparin. Effects of pH. Biochem J. 1985 Mar 1;226(2):409–413. doi: 10.1042/bj2260409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bessesen D. H., Robertson A. D., Eckel R. H. Weight reduction increases adipose but decreases cardiac LPL in reduced-obese Zucker rats. Am J Physiol. 1991 Aug;261(2 Pt 1):E246–E251. doi: 10.1152/ajpendo.1991.261.2.E246. [DOI] [PubMed] [Google Scholar]
  8. Camps L., Reina M., Llobera M., Bengtsson-Olivecrona G., Olivecrona T., Vilaró S. Lipoprotein lipase in lungs, spleen, and liver: synthesis and distribution. J Lipid Res. 1991 Dec;32(12):1877–1888. [PubMed] [Google Scholar]
  9. Chajek-Shaul T., Friedman G., Ziv E., Bar-On H., Bengtsson-Olivecrona G. Fate of lipoprotein lipase taken up by the rat liver. Evidence for a conformational change with loss of catalytic activity. Biochim Biophys Acta. 1988 Nov 25;963(2):183–191. doi: 10.1016/0005-2760(88)90279-2. [DOI] [PubMed] [Google Scholar]
  10. Davis R. C., Ben-Zeev O., Martin D., Doolittle M. H. Combined lipase deficiency in the mouse. Evidence of impaired lipase processing and secretion. J Biol Chem. 1990 Oct 15;265(29):17960–17966. [PubMed] [Google Scholar]
  11. Doolittle M. H., Ben-Zeev O., Elovson J., Martin D., Kirchgessner T. G. The response of lipoprotein lipase to feeding and fasting. Evidence for posttranslational regulation. J Biol Chem. 1990 Mar 15;265(8):4570–4577. [PubMed] [Google Scholar]
  12. Eckel R. H. Lipoprotein lipase. A multifunctional enzyme relevant to common metabolic diseases. N Engl J Med. 1989 Apr 20;320(16):1060–1068. doi: 10.1056/NEJM198904203201607. [DOI] [PubMed] [Google Scholar]
  13. Enerbäck S., Semb H., Tavernier J., Bjursell G., Olivecrona T. Tissue-specific regulation of guinea pig lipoprotein lipase; effects of nutritional state and of tumor necrosis factor on mRNA levels in adipose tissue, heart and liver. Gene. 1988 Apr 15;64(1):97–106. doi: 10.1016/0378-1119(88)90484-2. [DOI] [PubMed] [Google Scholar]
  14. Friedman G., Barak V., Chajek-Shaul T., Etienne J., Treves A. J., Stein O., Stein Y. Recombinant human interleukin-1 suppresses lipoprotein lipase activity, but not expression of lipoprotein lipase mRNA in mesenchymal rat heart cell cultures. Biochim Biophys Acta. 1991 May 2;1089(1):83–87. doi: 10.1016/0167-4781(91)90088-4. [DOI] [PubMed] [Google Scholar]
  15. Goldberg I. J., Soprano D. R., Wyatt M. L., Vanni T. M., Kirchgessner T. G., Schotz M. C. Localization of lipoprotein lipase mRNA in selected rat tissues. J Lipid Res. 1989 Oct;30(10):1569–1577. [PubMed] [Google Scholar]
  16. Hata A., Ridinger D. N., Sutherland S. D., Emi M., Kwong L. K., Shuhua J., Lubbers A., Guy-Grand B., Basdevant A., Iverius P. H. Missense mutations in exon 5 of the human lipoprotein lipase gene. Inactivation correlates with loss of dimerization. J Biol Chem. 1992 Oct 5;267(28):20132–20139. [PubMed] [Google Scholar]
  17. Hata A., Ridinger D. N., Sutherland S., Emi M., Shuhua Z., Myers R. L., Ren K., Cheng T., Inoue I., Wilson D. E. Binding of lipoprotein lipase to heparin. Identification of five critical residues in two distinct segments of the amino-terminal domain. J Biol Chem. 1993 Apr 25;268(12):8447–8457. [PubMed] [Google Scholar]
  18. Iverius P. H. Coupling of glycosaminoglycans to agarose beads (sepharose 4B). Biochem J. 1971 Oct;124(4):677–683. doi: 10.1042/bj1240677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Iverius P. H., Ostlund-Lindqvist A. M. Lipoprotein lipase from bovine milk. Isolation procedure, chemical characterization, and molecular weight analysis. J Biol Chem. 1976 Dec 25;251(24):7791–7795. [PubMed] [Google Scholar]
  20. Khoo J. C., Mahoney E. M., Witztum J. L. Secretion of lipoprotein lipase by macrophages in culture. J Biol Chem. 1981 Jul 25;256(14):7105–7108. [PubMed] [Google Scholar]
  21. Liu G., Bengtsson-Olivecrona G., Olivecrona T. Assembly of lipoprotein lipase in perfused guinea-pig hearts. Biochem J. 1993 May 15;292(Pt 1):277–282. doi: 10.1042/bj2920277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Liu G., Olivecrona T. Synthesis and transport of lipoprotein lipase in perfused guinea pig hearts. Am J Physiol. 1992 Aug;263(2 Pt 2):H438–H446. doi: 10.1152/ajpheart.1992.263.2.H438. [DOI] [PubMed] [Google Scholar]
  23. Liu M. S., Ma Y., Hayden M. R., Brunzell J. D. Mapping of the epitope on lipoprotein lipase recognized by a monoclonal antibody (5D2) which inhibits lipase activity. Biochim Biophys Acta. 1992 Sep 22;1128(1):113–115. doi: 10.1016/0005-2760(92)90264-v. [DOI] [PubMed] [Google Scholar]
  24. Masuno H., Blanchette-Mackie E. J., Chernick S. S., Scow R. O. Synthesis of inactive nonsecretable high mannose-type lipoprotein lipase by cultured brown adipocytes of combined lipase-deficient cld/cld mice. J Biol Chem. 1990 Jan 25;265(3):1628–1638. [PubMed] [Google Scholar]
  25. Okabe T., Yorifuji H., Murase T., Takaku F. Pulmonary macrophage: a major source of lipoprotein lipase in the lung. Biochem Biophys Res Commun. 1984 Nov 30;125(1):273–278. doi: 10.1016/s0006-291x(84)80364-2. [DOI] [PubMed] [Google Scholar]
  26. Olivecrona T., Bengtsson G. Immunochemical properties of lipoprotein lipase. Development of an immunoassay applicable to several mammalian species. Biochim Biophys Acta. 1983 Jun 16;752(1):38–45. doi: 10.1016/0005-2760(83)90230-8. [DOI] [PubMed] [Google Scholar]
  27. Olivecrona T., Chernick S. S., Bengtsson-Olivecrona G., Garrison M., Scow R. O. Synthesis and secretion of lipoprotein lipase in 3T3-L1 adipocytes. Demonstration of inactive forms of lipase in cells. J Biol Chem. 1987 Aug 5;262(22):10748–10759. [PubMed] [Google Scholar]
  28. Ong J. M., Kern P. A. Effect of feeding and obesity on lipoprotein lipase activity, immunoreactive protein, and messenger RNA levels in human adipose tissue. J Clin Invest. 1989 Jul;84(1):305–311. doi: 10.1172/JCI114155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Osborne J. C., Jr, Bengtsson-Olivecrona G., Lee N. S., Olivecrona T. Studies on inactivation of lipoprotein lipase: role of the dimer to monomer dissociation. Biochemistry. 1985 Sep 24;24(20):5606–5611. doi: 10.1021/bi00341a048. [DOI] [PubMed] [Google Scholar]
  30. Ottosson M., Vikman-Adolfsson K., Enerbäck S., Olivecrona G., Björntorp P. The effects of cortisol on the regulation of lipoprotein lipase activity in human adipose tissue. J Clin Endocrinol Metab. 1994 Sep;79(3):820–825. doi: 10.1210/jcem.79.3.8077367. [DOI] [PubMed] [Google Scholar]
  31. Park J. W., Oh M. S., Yang J. Y., Park B. H., Rho H. W., Lim S. N., Jhee E. C., Kim H. R. Glycosylation, dimerization, and heparin affinity of lipoprotein lipase in 3T3-L1 adipocytes. Biochim Biophys Acta. 1995 Jan 3;1254(1):45–50. doi: 10.1016/0005-2760(94)00161-q. [DOI] [PubMed] [Google Scholar]
  32. Peterson J., Fujimoto W. Y., Brunzell J. D. Human lipoprotein lipase: relationship of activity, heparin affinity, and conformation as studied with monoclonal antibodies. J Lipid Res. 1992 Aug;33(8):1165–1170. [PubMed] [Google Scholar]
  33. Semb H., Olivecrona T. Two different mechanisms are involved in nutritional regulation of lipoprotein lipase in guinea-pig adipose tissue. Biochem J. 1989 Sep 1;262(2):505–511. doi: 10.1042/bj2620505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Simsolo R. B., Ong J. M., Saffari B., Kern P. A. Effect of improved diabetes control on the expression of lipoprotein lipase in human adipose tissue. J Lipid Res. 1992 Jan;33(1):89–95. [PubMed] [Google Scholar]
  35. Tan M. H., Sata T., Havel R. J. The significance of lipoprotein lipase in rat skeletal muscles. J Lipid Res. 1977 May;18(3):363–370. [PubMed] [Google Scholar]
  36. Tavangar K., Murata Y., Patel S., Kalinyak J. E., Pedersen M. E., Goers J. F., Hoffman A. R., Kraemer F. B. Developmental regulation of lipoprotein lipase in rats. Am J Physiol. 1992 Mar;262(3 Pt 1):E330–E337. doi: 10.1152/ajpendo.1992.262.3.E330. [DOI] [PubMed] [Google Scholar]
  37. Tavangar K., Murata Y., Pedersen M. E., Goers J. F., Hoffman A. R., Kraemer F. B. Regulation of lipoprotein lipase in the diabetic rat. J Clin Invest. 1992 Nov;90(5):1672–1678. doi: 10.1172/JCI116039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Vannier C., Amri E. Z., Etienne J., Négrel R., Ailhaud G. Maturation and secretion of lipoprotein lipase in cultured adipose cells. I. Intracellular activation of the enzyme. J Biol Chem. 1985 Apr 10;260(7):4424–4431. [PubMed] [Google Scholar]
  39. Vilaró S., Camps L., Reina M., Perez-Clausell J., Llobera M., Olivecrona T. Localization of lipoprotein lipase to discrete areas of the guinea pig brain. Brain Res. 1990 Jan 8;506(2):249–253. doi: 10.1016/0006-8993(90)91258-i. [DOI] [PubMed] [Google Scholar]
  40. Vilaró S., Llobera M., Bengtsson-Olivecrona G., Olivecrona T. Synthesis of lipoprotein lipase in the liver of newborn rats and localization of the enzyme by immunofluorescence. Biochem J. 1988 Jan 15;249(2):549–556. doi: 10.1042/bj2490549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Vilella E., Joven J., Fernández M., Vilaró S., Brunzell J. D., Olivecrona T., Bengtsson-Olivecrona G. Lipoprotein lipase in human plasma is mainly inactive and associated with cholesterol-rich lipoproteins. J Lipid Res. 1993 Sep;34(9):1555–1564. [PubMed] [Google Scholar]
  42. Wallinder L., Bengtsson G., Olivecrona T. Rapid removal to the liver of intravenously injected lipoprotein lipase. Biochim Biophys Acta. 1979 Oct 26;575(1):166–173. doi: 10.1016/0005-2760(79)90142-5. [DOI] [PubMed] [Google Scholar]
  43. Wallinder L., Peterson J., Olivecrona T., Bengtsson-Olivecrona G. Hepatic and extrahepatic uptake of intravenously injected lipoprotein lipase. Biochim Biophys Acta. 1984 Oct 4;795(3):513–524. doi: 10.1016/0005-2760(84)90181-4. [DOI] [PubMed] [Google Scholar]

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