The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Lipc  -  lipase, hepatic

Mus musculus

Synonyms: AI256194, HL, Hepatic lipase, Hepatic triacylglycerol lipase, Hpl, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Lipc

  • DISCUSSION: This use of reciprocal hemizygosity analysis in mammals, which, to our knowledge, is the first reported, reveals its power to detect previously unknown effects of Lipc on obesity [1].
  • Mice doubly deficient in apo E and hepatic lipase have more pronounced hypercholesterolemia, even though remnants do not accumulate appreciably in mice deficient in hepatic lipase alone [2].
  • Mild dyslipidemia in mice following targeted inactivation of the hepatic lipase gene [3].
  • In these mice, hypertriglyceridemia results from the inhibition of lipoprotein lipase and hepatic lipase activities by hapoA-II carried on VLDL [4].
  • We have investigated the role of hepatic lipase (HL) in remnant lipoprotein metabolism independent of lipolysis by using recombinant adenovirus to express native and catalytically inactive HL (HL-145G) in apolipoprotein (apo)E-deficient mice characterized by increased plasma concentrations of apoB-48-containing remnants [5].

High impact information on Lipc

  • This is most likely due to reduced activity of the HDL-catabolic enzyme hepatic lipase (Lipc) and increased expression of HDL-cholesterol esterifying enzyme lecithin:cholesterol acyl transferase (Lcat) [6].
  • We found that expression of HL by macrophages enhances early aortic lesion formation in both apoE-KO and LCAT-Tg mice, without changing the plasma lipid profile, lipoprotein lipid composition, or HL and lipoprotein lipase activities [7].
  • Hepatic lipase expression in macrophages contributes to atherosclerosis in apoE-deficient and LCAT-transgenic mice [7].
  • HL does, however, enhance oxidized LDL uptake by peritoneal macrophages [7].
  • We used bone marrow transplantation (BMT) to generate apoE-KO and apoE-KO x HL-KO mice, as well as LCAT-Tg and LCAT-Tg x HL-KO mice, chimeric for macrophage HL gene expression [7].

Chemical compound and disease context of Lipc


Biological context of Lipc

  • No interaction between Lipc and chromosome 7 was demonstrated [1].
  • The CLD mutation allows synthesis and glycosylation of HL, but blocks activation of the lipase [9].
  • We have further characterized the abnormal lipoprotein phenotype in young hepatic lipase-deficient mice and have found more pronounced elevations of high density lipoproteins associated in particular with a 5-fold increase in plasma concentrations of apolipoprotein E [10].
  • Hepatic lipase may prevent such vesicular lipoproteins from accumulating in apo E-deficient mice by hydrolyzing phosphatidyl choline as scavenger receptor B1 removes the cholesteryl esters and by gradual endocytosis of lipoproteins bound to hepatic lipase on the surface of hepatocytes [2].
  • To extend this observation, the HL transgene was expressed in human apoB transgenic (huBTg) and apoE-deficient (apoE-/-) mice, both of which have high plasma levels of apoB-containing lipoproteins [11].

Anatomical context of Lipc


Associations of Lipc with chemical compounds

  • RESULTS: We show here that mice lacking both endogenous HL and LDL receptor (HL-/-:LDLR-/-) dramatically increased their plasma triglyceride-rich lipoproteins and their remnants as a consequence of reduced liver uptake [15].
  • Heparin had no significant effect on plasma hepatic lipase activity in defective mice [16].
  • Mice lacking both HL and apoE (hhee) have a plasma total cholesterol of 917 +/- 252 mg/dl (n = 24), which is 184% that of mice lacking only apoE (HHee; 497 +/- 161 mg/dl, n = 20, p < 0. 001) [17].
  • Attenuated corticosterone response to chronic ACTH stimulation in hepatic lipase-deficient mice: evidence for a role for hepatic lipase in adrenal physiology [18].
  • Fenofibrate did not induce any change in hepatic lipase activity [19].

Regulatory relationships of Lipc

  • These findings indicate that SR-BI expression may be influenced by changes in HL activity [14].
  • HL knockout mice had a similar prevalence of gallstone formation as compared with control mice when both strains were fed with a lithogenic diet [20].
  • Pre-injection of lactoferrin into normal mice inhibited the plasma clearance of both non-lipolyzed chylomicrons and chylomicrons lipolyzed by HL [21].

Other interactions of Lipc

  • Thus, the cld mutation appears not to globally disrupt the secretion of all N-linked glycoproteins, but rather selectively impairs LPL and HL at points essential to their normal intracellular transport and secretion [22].
  • Combined hyperlipidemia/hyperalphalipoproteinemia associated with premature spontaneous atherosclerosis in mice lacking hepatic lipase and low density lipoprotein receptor [15].
  • Thus, the CLD mutation allows secretion of inactive HL by liver and adrenals [9].
  • Our findings indicate that LPL, HL and pancreatic lipase, although closely related, are processed differently [9].
  • The action of hepatic lipase on apoA-I-containing lipoproteins may facilitate the SR-BI-mediated uptake of HDL lipid [23].

Analytical, diagnostic and therapeutic context of Lipc


  1. Reciprocal hemizygosity analysis of mouse hepatic lipase reveals influence on obesity. Farahani, P., Fisler, J.S., Wong, H., Diament, A.L., Yi, N., Warden, C.H. Obes. Res. (2004) [Pubmed]
  2. Lamellar lipoproteins uniquely contribute to hyperlipidemia in mice doubly deficient in apolipoprotein E and hepatic lipase. Bergeron, N., Kotite, L., Verges, M., Blanche, P., Hamilton, R.L., Krauss, R.M., Bensadoun, A., Havel, R.J. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  3. Mild dyslipidemia in mice following targeted inactivation of the hepatic lipase gene. Homanics, G.E., de Silva, H.V., Osada, J., Zhang, S.H., Wong, H., Borensztajn, J., Maeda, N. J. Biol. Chem. (1995) [Pubmed]
  4. Human apolipoprotein A-II associates with triglyceride-rich lipoproteins in plasma and impairs their catabolism. Dugu??-Pujol, S., Rousset, X., Pastier, D., Quang, N.T., Pautre, V., Chambaz, J., Chabert, M., Kalopissis, A.D. J. Lipid Res. (2006) [Pubmed]
  5. Hepatic lipase facilitates the selective uptake of cholesteryl esters from remnant lipoproteins in apoE-deficient mice. Amar, M.J., Dugi, K.A., Haudenschild, C.C., Shamburek, R.D., Foger, B., Chase, M., Bensadoun, A., Hoyt, R.F., Brewer, H.B., Santamarina-Fojo, S. J. Lipid Res. (1998) [Pubmed]
  6. Hepatocyte nuclear factor-1alpha is an essential regulator of bile acid and plasma cholesterol metabolism. Shih, D.Q., Bussen, M., Sehayek, E., Ananthanarayanan, M., Shneider, B.L., Suchy, F.J., Shefer, S., Bollileni, J.S., Gonzalez, F.J., Breslow, J.L., Stoffel, M. Nat. Genet. (2001) [Pubmed]
  7. Hepatic lipase expression in macrophages contributes to atherosclerosis in apoE-deficient and LCAT-transgenic mice. Nong, Z., Gonzalez-Navarro, H., Amar, M., Freeman, L., Knapper, C., Neufeld, E.B., Paigen, B.J., Hoyt, R.F., Fruchart-Najib, J., Santamarina-Fojo, S. J. Clin. Invest. (2003) [Pubmed]
  8. Identification of four chromosomal loci determining obesity in a multifactorial mouse model. Warden, C.H., Fisler, J.S., Shoemaker, S.M., Wen, P.Z., Svenson, K.L., Pace, M.J., Lusis, A.J. J. Clin. Invest. (1995) [Pubmed]
  9. 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]
  10. Metabolism of lipoproteins containing apolipoprotein B in hepatic lipase-deficient mice. Qiu, S., Bergeron, N., Kotite, L., Krauss, R.M., Bensadoun, A., Havel, R.J. J. Lipid Res. (1998) [Pubmed]
  11. Overexpression of hepatic lipase in transgenic mice decreases apolipoprotein B-containing and high density lipoproteins. Evidence that hepatic lipase acts as a ligand for lipoprotein uptake. Dichek, H.L., Brecht, W., Fan, J., Ji, Z.S., McCormick, S.P., Akeefe, H., Conzo, L., Sanan, D.A., Weisgraber, K.H., Young, S.G., Taylor, J.M., Mahley, R.W. J. Biol. Chem. (1998) [Pubmed]
  12. 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]
  13. Genetic loci controlling body fat, lipoprotein metabolism, and insulin levels in a multifactorial mouse model. Mehrabian, M., Wen, P.Z., Fisler, J., Davis, R.C., Lusis, A.J. J. Clin. Invest. (1998) [Pubmed]
  14. Induction of adrenal scavenger receptor BI and increased high density lipoprotein-cholesteryl ether uptake by in vivo inhibition of hepatic lipase. Vieira-van Bruggen, D., Kalkman, I., van Gent, T., van Tol, A., Jansen, H. J. Biol. Chem. (1998) [Pubmed]
  15. Combined hyperlipidemia/hyperalphalipoproteinemia associated with premature spontaneous atherosclerosis in mice lacking hepatic lipase and low density lipoprotein receptor. Barcat, D., Amadio, A., Palos-Pinto, A., Daret, D., Benlian, P., Darmon, M., Bérard, A.M. Atherosclerosis (2006) [Pubmed]
  16. Effect of combined lipase deficiency (cld/cld) on hepatic and lipoprotein lipase activities in liver and plasma of newborn mice. Olivecrona, T., Bengtsson-Olivecrona, G., Chernick, S.S., Scow, R.O. Biochim. Biophys. Acta (1986) [Pubmed]
  17. Hepatic lipase deficiency increases plasma cholesterol but reduces susceptibility to atherosclerosis in apolipoprotein E-deficient mice. Mezdour, H., Jones, R., Dengremont, C., Castro, G., Maeda, N. J. Biol. Chem. (1997) [Pubmed]
  18. Attenuated corticosterone response to chronic ACTH stimulation in hepatic lipase-deficient mice: evidence for a role for hepatic lipase in adrenal physiology. Dichek, H.L., Agrawal, N., Andaloussi, N.E., Qian, K. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  19. Induction of the phospholipid transfer protein gene accounts for the high density lipoprotein enlargement in mice treated with fenofibrate. Bouly, M., Masson, D., Gross, B., Jiang , X.C., Fievet, C., Castro, G., Tall, A.R., Fruchart, J.C., Staels, B., Lagrost, L., Luc, G. J. Biol. Chem. (2001) [Pubmed]
  20. Biliary lipid secretion, bile acid metabolism, and gallstone formation are not impaired in hepatic lipase-deficient mice. Amigo, L., Mardones, P., Ferrada, C., Zanlungo, S., Nervi, F., Miquel, J.F., Rigotti, A. Hepatology (2003) [Pubmed]
  21. Plasma clearance and liver uptake of chylomicron remnants generated by hepatic lipase lipolysis: evidence for a lactoferrin-sensitive and apolipoprotein E-independent pathway. Crawford, S.E., Borensztajn, J. J. Lipid Res. (1999) [Pubmed]
  22. 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]
  23. Scavenger receptor BI (SR-BI) is up-regulated in adrenal gland in apolipoprotein A-I and hepatic lipase knock-out mice as a response to depletion of cholesterol stores. In vivo evidence that SR-BI is a functional high density lipoprotein receptor under feedback control. Wang, N., Weng, W., Breslow, J.L., Tall, A.R. J. Biol. Chem. (1996) [Pubmed]
  24. 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]
  25. Effect of acute Chlamydia pneumoniae infection on lipoprotein metabolism in NIH/S mice. Tiirola, T., Erkkilä, L., Laitinen, K., Leinonen, M., Saikku, P., Bloigu, A., Jauhiainen, M. Scand. J. Clin. Lab. Invest. (2002) [Pubmed]
WikiGenes - Universities