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Gene Review

Lpl  -  lipoprotein lipase

Mus musculus

Synonyms: LPL, Lipoprotein lipase, O 1-4-5
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Disease relevance of Lpl

  • Increased LPL activity completely normalized hypertriglyceridemia of apoa5-deficient mice; however, overexpression of human apoAV modulated triglyceride levels only slightly when LPL was reduced [1].
  • Taken together, these data indicate that macrophage LPL expression in the artery wall promotes atherogenesis during foam cell lesion formation, but this impact may be limited to macrophage-rich lesions [2].
  • Although both groups developed hypercholesterolemia to a comparable degree in response to an atherogenic diet, the LPL/APOEKO mice developed 2-fold smaller fatty streak lesions in the aortic sinus compared to the APOEKO mice [3].
  • After eating an atherogenic diet, LPL+/- as compared to LPL+/+ mice have more dyslipidemia, but no more atherosclerosis, and less LPL protein in atherosclerotic lesions [4].
  • Remarkably, after focal cerebral ischemia, the expression of EL was unaffected whereas a dramatic increase in LPL expression was observed in neocortical areas of the lesioned side of the brain [5].

High impact information on Lpl

  • Chylomicrons formed in the intestinal mucosa during the absorption of the products of digestion, are processed by the peripheral circulation by lipoprotein lipase, which catalyses the breakdown of triglycerides in chylomicrons to free fatty acids and glycerol [6].
  • We have found previously that macrophages secrete the hormone cachectin, which specifically suppresses LPL activity in cultured adipocytes (3T3-L1 cells) [7].
  • Among these changes, a hypertriglyceridaemic state is frequently evident, resulting from defective triglyceride clearance, caused by systemic suppression of the enzyme lipoprotein lipase (LPL) [7].
  • A single recessive mutation, cld, on mouse chromosome 17 causes an apparent deficiency of both lipoprotein lipase and hepatic triglyceride lipase activities [8].
  • The factor(s) secreted by fully activated macrophages that inhibited LPL secretion was shown to be thermolabile and distinct from tumor necrosis factor [9].

Chemical compound and disease context of Lpl


Biological context of Lpl


Anatomical context of Lpl

  • In contrast, mouse AT and isolated adipocytes that lacked LPL expressed large amounts of EL mRNA [17].
  • Endothelial lipase provides an alternative pathway for FFA uptake in lipoprotein lipase-deficient mouse adipose tissue [17].
  • After 19 weeks of diet, the lesions in the proximal aorta were complex with relatively few macrophages expressing LPL protein and mRNA in LPL(+/+) --> LDLR(-/-) mice [2].
  • Decreased plasma NEFA and TG levels in fasted HSL-ko mice were associated with increased fractional catabolic rates of VLDL-TG and an induction of the tissue-specific lipoprotein lipase (LPL) activity in cardiac muscle, skeletal muscle, and white AT [18].
  • Both increased VLDL fractional catabolic rates and increased LPL activity in muscle were unable to provide the heart with sufficient NEFA, which led to decreased tissue TG levels in cardiac muscle [18].

Associations of Lpl with chemical compounds

  • On a normal chow diet, LPL/LDLRKO mice showed marked suppression of mean plasma triglyceride levels (32 versus 236 mg/dl) and modest decrease in mean cholesterol levels (300 versus 386 mg/dl) as compared with LDLRKO mice [14].
  • Hearts from 3-month-old mice expressing GPI-anchored human LpL (hLpLGPI) mice had increased fatty acid oxidation and heart failure genes and decreased glucose transporter genes [19].
  • More luminal, lipid-laden macrophages generally did not stain for LPL, but deeper, lipid-poor macrophages as well as necrotic core regions contained immunoreactive LPL [4].
  • Immunofluorescent LPL was not found in normal newborn liver cells unless the cells were treated with monensin, thus demonstrating that normal liver cells synthesized and secreted LPL [20].
  • Upregulation of LDLR by lipoprotein-deficient serum/lovastatin in wild-type cells resulted in a 7-fold increase of LPL-mediated LDL uptake [21].

Physical interactions of Lpl


Regulatory relationships of Lpl


Other interactions of Lpl


Analytical, diagnostic and therapeutic context of Lpl


  1. Apolipoprotein AV accelerates plasma hydrolysis of triglyceride-rich lipoproteins by interaction with proteoglycan-bound lipoprotein lipase. Merkel, M., Loeffler, B., Kluger, M., Fabig, N., Geppert, G., Pennacchio, L.A., Laatsch, A., Heeren, J. J. Biol. Chem. (2005) [Pubmed]
  2. Macrophage lipoprotein lipase promotes foam cell formation and atherosclerosis in low density lipoprotein receptor-deficient mice. Babaev, V.R., Patel, M.B., Semenkovich, C.F., Fazio, S., Linton, M.F. J. Biol. Chem. (2000) [Pubmed]
  3. Overexpressed lipoprotein lipase protects against atherosclerosis in apolipoprotein E knockout mice. Yagyu, H., Ishibashi, S., Chen, Z., Osuga, J., Okazaki, M., Perrey, S., Kitamine, T., Shimada, M., Ohashi, K., Harada, K., Shionoiri, F., Yahagi, N., Gotoda, T., Yazaki, Y., Yamada, N. J. Lipid Res. (1999) [Pubmed]
  4. Effects of heterozygous lipoprotein lipase deficiency on diet-induced atherosclerosis in mice. Semenkovich, C.F., Coleman, T., Daugherty, A. J. Lipid Res. (1998) [Pubmed]
  5. Lipoprotein lipase and endothelial lipase expression in mouse brain: regional distribution and selective induction following kainic acid-induced lesion and focal cerebral ischemia. Paradis, E., Clavel, S., Julien, P., Murthy, M.R., de Bilbao, F., Arsenijevic, D., Giannakopoulos, P., Vallet, P., Richard, D. Neurobiol. Dis. (2004) [Pubmed]
  6. The LDL-receptor-related protein, LRP, is an apolipoprotein E-binding protein. Beisiegel, U., Weber, W., Ihrke, G., Herz, J., Stanley, K.K. Nature (1989) [Pubmed]
  7. Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Beutler, B., Greenwald, D., Hulmes, J.D., Chang, M., Pan, Y.C., Mathison, J., Ulevitch, R., Cerami, A. Nature (1985) [Pubmed]
  8. Combined lipase deficiency (cld): a lethal mutation on chromosome 17 of the mouse. Paterniti, J.R., Brown, W.V., Ginsberg, H.N., Artzt, K. Science (1983) [Pubmed]
  9. Effects of activation on lipoprotein lipase secretion by macrophages. Evidence for autoregulation. Behr, S.R., Kraemer, F.B. J. Exp. Med. (1986) [Pubmed]
  10. The P-407-induced murine model of dose-controlled hyperlipidemia and atherosclerosis: a review of findings to date. Johnston, T.P. J. Cardiovasc. Pharmacol. (2004) [Pubmed]
  11. Low-density lipoprotein receptor-related protein/alpha 2-macroglobulin receptor on murine peritoneal macrophages mediates the binding and catabolism of low-density lipoprotein. Wu, S.M., Pizzo, S.V. Arch. Biochem. Biophys. (1996) [Pubmed]
  12. Severe hypertriglyceridemia, reduced high density lipoprotein, and neonatal death in lipoprotein lipase knockout mice. Mild hypertriglyceridemia with impaired very low density lipoprotein clearance in heterozygotes. Weinstock, P.H., Bisgaier, C.L., Aalto-Setälä, K., Radner, H., Ramakrishnan, R., Levak-Frank, S., Essenburg, A.D., Zechner, R., Breslow, J.L. J. Clin. Invest. (1995) [Pubmed]
  13. Retinoid X receptor gamma-deficient mice have increased skeletal muscle lipoprotein lipase activity and less weight gain when fed a high-fat diet. Haugen, B.R., Jensen, D.R., Sharma, V., Pulawa, L.K., Hays, W.R., Krezel, W., Chambon, P., Eckel, R.H. Endocrinology (2004) [Pubmed]
  14. Suppression of diet-induced atherosclerosis in low density lipoprotein receptor knockout mice overexpressing lipoprotein lipase. Shimada, M., Ishibashi, S., Inaba, T., Yagyu, H., Harada, K., Osuga, J.I., Ohashi, K., Yazaki, Y., Yamada, N. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  15. Genetic and developmental regulation of the lipoprotein lipase gene: loci both distal and proximal to the lipoprotein lipase structural gene control enzyme expression. Kirchgessner, T.G., LeBoeuf, R.C., Langner, C.A., Zollman, S., Chang, C.H., Taylor, B.A., Schotz, M.C., Gordon, J.I., Lusis, A.J. J. Biol. Chem. (1989) [Pubmed]
  16. Regulation of lipoprotein lipase by protein kinase C alpha in 3T3-F442A adipocytes. Ranganathan, G., Song, W., Dean, N., Monia, B., Barger, S.W., Kern, P.A. J. Biol. Chem. (2002) [Pubmed]
  17. Endothelial lipase provides an alternative pathway for FFA uptake in lipoprotein lipase-deficient mouse adipose tissue. Kratky, D., Zimmermann, R., Wagner, E.M., Strauss, J.G., Jin, W., Kostner, G.M., Haemmerle, G., Rader, D.J., Zechner, R. J. Clin. Invest. (2005) [Pubmed]
  18. Hormone-sensitive lipase deficiency in mice changes the plasma lipid profile by affecting the tissue-specific expression pattern of lipoprotein lipase in adipose tissue and muscle. Haemmerle, G., Zimmermann, R., Strauss, J.G., Kratky, D., Riederer, M., Knipping, G., Zechner, R. J. Biol. Chem. (2002) [Pubmed]
  19. Apolipoprotein B production reduces lipotoxic cardiomyopathy: studies in heart-specific lipoprotein lipase transgenic mouse. Yokoyama, M., Yagyu, H., Hu, Y., Seo, T., Hirata, K., Homma, S., Goldberg, I.J. J. Biol. Chem. (2004) [Pubmed]
  20. Adrenal and liver in normal and cld/cld mice synthesize and secrete hepatic lipase, but the lipase is inactive in cld/cld mice. Schultz, C.J., Blanchette-Mackie, E.J., Scow, R.O. J. Lipid Res. (2000) [Pubmed]
  21. Lipoprotein lipase-facilitated uptake of LDL is mediated by the LDL receptor. Loeffler, B., Heeren, J., Blaeser, M., Radner, H., Kayser, D., Aydin, B., Merkel, M. J. Lipid Res. (2007) [Pubmed]
  22. Induction of tumor necrosis factor alpha gene expression by lipoprotein lipase. Renier, G., Skamene, E., DeSanctis, J.B., Radzioch, D. J. Lipid Res. (1994) [Pubmed]
  23. STAT 1 binds to the LPL promoter in vitro. Hogan, J.C., Stephens, J.M. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  24. Binding of beta-VLDL to heparan sulfate proteoglycans requires lipoprotein lipase, whereas ApoE only modulates binding affinity. de Beer, F., Hendriks, W.L., van Vark, L.C., Kamerling, S.W., van Dijk, K.W., Hofker, M.H., Smelt, A.H., Havekes, L.M. Arterioscler. Thromb. Vasc. Biol. (1999) [Pubmed]
  25. Angptl3-null mice show low plasma lipid concentrations by enhanced lipoprotein lipase activity. Fujimoto, K., Koishi, R., Shimizugawa, T., Ando, Y. Exp. Anim. (2006) [Pubmed]
  26. ApoAV reduces plasma triglycerides by inhibiting very low density lipoprotein-triglyceride (VLDL-TG) production and stimulating lipoprotein lipase-mediated VLDL-TG hydrolysis. Schaap, F.G., Rensen, P.C., Voshol, P.J., Vrins, C., van der Vliet, H.N., Chamuleau, R.A., Havekes, L.M., Groen, A.K., van Dijk, K.W. J. Biol. Chem. (2004) [Pubmed]
  27. Combined lipase deficiency in the mouse. Evidence of impaired lipase processing and secretion. Davis, R.C., Ben-Zeev, O., Martin, D., Doolittle, M.H. J. Biol. Chem. (1990) [Pubmed]
  28. Lipoprotein lipase mRNA in neonatal and adult mouse tissues: comparison of normal and combined lipase deficiency (cld) mice assessed by in situ hybridization. Yacoub, L.K., Vanni, T.M., Goldberg, I.J. J. Lipid Res. (1990) [Pubmed]
  29. Expression in mouse embryos and in adult mouse brain of three members of the amyloid precursor protein family, of the alpha-2-macroglobulin receptor/low density lipoprotein receptor-related protein and of its ligands apolipoprotein E, lipoprotein lipase, alpha-2-macroglobulin and the 40,000 molecular weight receptor-associated protein. Lorent, K., Overbergh, L., Moechars, D., De Strooper, B., Van Leuven, F., Van den Berghe, H. Neuroscience (1995) [Pubmed]
  30. Abnormal patterns of lipoprotein lipase release into the plasma in GPIHBP1-deficient mice. Weinstein, M.M., Yin, L., Beigneux, A.P., Davies, B.S., Gin, P., Estrada, K., Melford, K., Bishop, J.R., Esko, J.D., Dallinga-Thie, G.M., Fong, L.G., Bensadoun, A., Young, S.G. J. Biol. Chem. (2008) [Pubmed]
  31. Atherosclerosis is enhanced by testosterone deficiency and attenuated by CETP expression in transgenic mice. Casquero, A.C., Berti, J.A., Salerno, A.G., Bighetti, E.J., Cazita, P.M., Ketelhuth, D.F., Gidlund, M., Oliveira, H.C. J. Lipid Res. (2006) [Pubmed]
  32. Combined lipase deficiency (cld/cld) in mice affects differently post-translational processing of lipoprotein lipase, hepatic lipase and pancreatic lipase. Scow, R.O., Schultz, C.J., Park, J.W., Blanchette-Mackie, E.J. Chem. Phys. Lipids (1998) [Pubmed]
  33. Tumor necrosis factor-alpha eliminates binding of NF-Y and an octamer-binding protein to the lipoprotein lipase promoter in 3T3-L1 adipocytes. Morin, C.L., Schlaepfer, I.R., Eckel, R.H. J. Clin. Invest. (1995) [Pubmed]
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