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Gene Review

LIPC  -  lipase, hepatic

Homo sapiens

Synonyms: HDLCQ12, HL, HTGL, Hepatic lipase, Hepatic triacylglycerol lipase, ...
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Disease relevance of LIPC

  • Ethnic differences in hepatic lipase and HDL in Japanese, black, and white Americans: role of central obesity and LIPC polymorphisms [1].
  • In the present study, we have investigated the effects of the CETP promoter -1337 C>T and LIPC promoter -514 C>T polymorphisms on serum lipid profiles and risk of coronary atherosclerosis in 206 patients (154 males) with heterozygous FH (familial hypercholesterolaemia) [2].
  • METHODS: Two genetic polymorphisms in LIPC (-514C-->T and +651A-->G) were determined by polymerase chain reaction and restriction analysis in 118 subjects of the ATOMIX (Atorvastatin in Mixed dyslipidemia) study who were randomized to treatment with either atorvastatin or bezafibrate and in 114 normolipidemic controls [3].
  • In this study, we found that LIPC -514TT genotype and overweight status, when occurring together, were associated with a 3-fold increase in risk of preeclampsia among Peruvian women [4].
  • HL (P < 0.05) and CETP activities (P < 0.05) were elevated in hyperthyroidism and reduced in hypothyroidism (P < 0.05, P < 0.01 respectively) and both were related to free T4 levels [5].

Psychiatry related information on LIPC

  • CONCLUSIONS: Regular moderate physical activity in patients with type 2 diabetes led to an overall increase in HL, LPL, and LCAT [6].
  • Acute alcohol withdrawal from a patient suffering from alcoholism with HLP led to a sharp increase of LPL with a simultaneous decrease of VLDL within 2 days and a more delayed increase of LDL, HDL2 and HTGL, all reaching normal values within 12 days after cessation of alcohol drinking [7].
  • We validate the association of LIPC promoter variation with fasting serum HDL-c and present data supporting an interaction with physical activity implying an increased effect on HDL-c in vigorous physically active subjects carrying the -250 A allele [8].

High impact information on LIPC


Chemical compound and disease context of LIPC


Biological context of LIPC


Anatomical context of LIPC

  • Hepatic lipase (HL) on the surface of hepatocytes and endothelial cells lining hepatic sinusoids, the adrenal glands, and the ovary hydrolyzes triglycerides and phospholipids of circulating lipoproteins [21].
  • 125I-Labeled HL is rapidly internalized and degraded by HepG2 cell lines, and approximately 70% of the cellular internalization and degradation is blocked by either exogenously added RAP or anti-LRP IgG [22].
  • Mouse fibroblasts that lack LRP display a greatly diminished capacity to internalize and degrade HL when compared to control fibroblasts [22].
  • HL activity was negatively correlated with total and coronary artery calcified lesion volume (r = -.55 to .57, P < .05) [23].
  • Effect of thyroid dysfunction on high-density lipoprotein subfraction metabolism: roles of hepatic lipase and cholesteryl ester transfer protein [5].

Associations of LIPC with chemical compounds

  • There was no consistent relationship between the population mean plasma HDL cholesterol concentration and the population LIPC -480T frequency [24].
  • However, we cannot exclude the participation of these genes, or the LIPC and LPL genes, as minor susceptibility loci in the expression of FCHL, or the TG or elevated total cholesterol (TC) traits in our families [25].
  • Common variation in promoters of both genes, LIPC -514C > T and APOC3 -482C > T, respectively, have been shown to affect plasma lipids and lipoproteins and glucose tolerance [26].
  • In summary, HDL metabolism was altered in thyroid dysfunction, and the effect of thyroid hormone on HDL was mediated mainly via its effect on HL activity [5].
  • Plasma activities of lipoprotein lipase, hepatic lipase and lecithin: cholesterol acyltransferase in patients considered for parenteral nutrition with fat emulsion [27].

Physical interactions of LIPC


Enzymatic interactions of LIPC

  • HTGL hydrolyzed triolein substrate at a rate much slower than LPL, and produced mainly free oleate with little monooleate [31].

Regulatory relationships of LIPC


Other interactions of LIPC

  • The latter correlated positively with LPL activity and HDL2 levels, and, inversely, with HL activity, lipemia, and triglyceride content of HDL2 [36].
  • There was no change in LPL, HTGL, or LCAT [37].
  • The effects of r-HDL morphology and size on HL activity were studied on r-HDL made of palmitoyloleoyl-PC, unesterified cholesterol, cholesteryl ester, and apolipoprotein AI [38].
  • ApoA-II appears to increase HL association with HDL and inhibits lipid hydrolysis [32].
  • Crosslinking experiments confirmed the binding of HL to LRP on the cell surface [39].

Analytical, diagnostic and therapeutic context of LIPC

  • Genotyping at position -250 of the LIPC gene was performed with PCR amplification, DraI enzyme digestion, and gel electrophoresis in 490 subjects with IGT whose DNA was available [40].
  • The higher HLA in the WA men remained after adjustment for the LIPC polymorphism's effect on HLA (P = 0.037) but was erased after adjustment for waist-to-hip-ratio (P = 0.46) [1].
  • No significant association was found between LIPC -480T and plasma HDL cholesterol or apolipoprotein AI concentration, after adjusting for covariates including gender and body mass index [24].
  • In cell culture experiments HL enhanced the uptake of 125I-LDL at both 4 and 37 degreesC [21].
  • Effects of hormone replacement therapy and hepatic lipase polymorphism on serum lipid profiles in postmenopausal Japanese women [41].


  1. Ethnic differences in hepatic lipase and HDL in Japanese, black, and white Americans: role of central obesity and LIPC polymorphisms. Carr, M.C., Brunzell, J.D., Deeb, S.S. J. Lipid Res. (2004) [Pubmed]
  2. CETP (cholesteryl ester transfer protein) promoter -1337 C>T polymorphism protects against coronary atherosclerosis in Japanese patients with heterozygous familial hypercholesterolaemia. Takata, M., Inazu, A., Katsuda, S., Miwa, K., Kawashiri, M.A., Nohara, A., Higashikata, T., Kobayashi, J., Mabuchi, H., Yamagishi, M. Clin. Sci. (2006) [Pubmed]
  3. Genetic variation in the hepatic lipase gene is associated with combined hyperlipidemia, plasma lipid concentrations, and lipid-lowering drug response. Cenarro, A., Artieda, M., Gonzalvo, C., Meriño-Ibarra, E., Arístegui, R., Gañán, A., Díaz, C., Sol, J.M., Pocoví, M., Civeira, F. Am. Heart J. (2005) [Pubmed]
  4. Hepatic lipase gene polymorphism, pre-pregnancy overweight status and risk of preeclampsia among Peruvian women. Enquobahrie, D.A., Sanchez, S.E., Muy-Rivera, M., Qiu, C., Zhang, C., Austin, M.A., Williams, M.A. Gynecol. Endocrinol. (2005) [Pubmed]
  5. Effect of thyroid dysfunction on high-density lipoprotein subfraction metabolism: roles of hepatic lipase and cholesteryl ester transfer protein. Tan, K.C., Shiu, S.W., Kung, A.W. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  6. Alterations of lipolytic enzymes and high-density lipoprotein subfractions induced by physical activity in type 2 diabetes mellitus. Lehmann, R., Engler, H., Honegger, R., Riesen, W., Spinas, G.A. Eur. J. Clin. Invest. (2001) [Pubmed]
  7. Post-heparin lipolytic activities and alterations of the chemical composition of high density lipoproteins in alcohol-induced type V hyperlipidemia. Breier, C., Lisch, H.J., Drexel, H., Braunsteiner, H. Atherosclerosis (1984) [Pubmed]
  8. The -250G>A promoter variant in hepatic lipase associates with elevated fasting serum high-density lipoprotein cholesterol modulated by interaction with physical activity in a study of 16,156 Danish subjects. Grarup, N., Andreasen, C.H., Andersen, M.K., Albrechtsen, A., Sandbaek, A., Lauritzen, T., Borch-Johnsen, K., Jørgensen, T., Schmitz, O., Hansen, T., Pedersen, O. J. Clin. Endocrinol. Metab. (2008) [Pubmed]
  9. Effect of oxandrolone treatment on the activity of lipoprotein lipase, hepatic lipase and phospholipase A1 of human postheparin plasma. Ehnholm, C., Huttunen, J.K., Kinnunen, P.J., Miettinen, T.A., Nikkilä, E.A. N. Engl. J. Med. (1975) [Pubmed]
  10. HDL in atherosclerosis: actor or bystander? Asztalos, B.F., Schaefer, E.J. Atherosclerosis. Supplements. (2003) [Pubmed]
  11. Environmental modulation of atherosclerosis end points in familial hypercholesterolemia. Hegele, R.A. Atherosclerosis. Supplements. (2002) [Pubmed]
  12. Association of variation in hepatic lipase activity with promoter variation in the hepatic lipase gene. The LOCAT Study Invsestigators. Tahvanainen, E., Syvanne, M., Frick, M.H., Murtomaki-Repo, S., Antikainen, M., Kesaniemi, Y.A., Kauma, H., Pasternak, A., Taskinen, M.R., Ehnholm, C. J. Clin. Invest. (1998) [Pubmed]
  13. Hepatic lipase and lipoprotein lipase in postheparin plasma in liver disease. relations to plasma proteins. Sauar, J., Skrede, S., Blomhoff, J.P. Clin. Chim. Acta (1978) [Pubmed]
  14. Role of lipases, lecithin:cholesterol acyltransferase and cholesteryl ester transfer protein in abnormal high density lipoprotein metabolism in insulin resistance and type 2 diabetes mellitus. de Vries, R., Borggreve, S.E., Dullaart, R.P. Clin. Lab. (2003) [Pubmed]
  15. Postheparin plasma lipoprotein lipase and hepatic lipase in diabetes mellitus. Relationship to plasma triglyceride metabolism. Nikkilä, E.A., Huttunen, J.K., Ehnholm, C. Diabetes (1977) [Pubmed]
  16. Increase in hepatic lipase activity after testosterone substitution in men with hypogonadism of pituitary origin. Valdemarsson, S., Hedner, P., Nilsson-Ehle, P. Acta medica Scandinavica. (1987) [Pubmed]
  17. Dyslipoproteinaemia in hypothyroidism of pituitary origin: effects of L-thyroxine substitution on lipoprotein lipase, hepatic lipase, and on plasma lipoproteins. Valdemarsson, S., Hedner, P., Nilsson-Ehle, P. Acta Endocrinol. (1983) [Pubmed]
  18. Hepatic lipase gene variant -514C>T is associated with lipoprotein and insulin sensitivity response to regular exercise: the HERITAGE Family Study. Teran-Garcia, M., Santoro, N., Rankinen, T., Bergeron, J., Rice, T., Leon, A.S., Rao, D.C., Skinner, J.S., Bergman, R.N., Després, J.P., Bouchard, C. Diabetes (2005) [Pubmed]
  19. Hepatic lipase: a marker for cardiovascular disease risk and response to therapy. Zambon, A., Deeb, S.S., Pauletto, P., Crepaldi, G., Brunzell, J.D. Curr. Opin. Lipidol. (2003) [Pubmed]
  20. Transcriptional regulation of the human hepatic lipase (LIPC) gene promoter. Rufibach, L.E., Duncan, S.A., Battle, M., Deeb, S.S. J. Lipid Res. (2006) [Pubmed]
  21. Interaction between ApoB and hepatic lipase mediates the uptake of ApoB-containing lipoproteins. Choi, S.Y., Goldberg, I.J., Curtiss, L.K., Cooper, A.D. J. Biol. Chem. (1998) [Pubmed]
  22. The cellular internalization and degradation of hepatic lipase is mediated by low density lipoprotein receptor-related protein and requires cell surface proteoglycans. Kounnas, M.Z., Chappell, D.A., Wong, H., Argraves, W.S., Strickland, D.K. J. Biol. Chem. (1995) [Pubmed]
  23. Lipoprotein lipase correlates positively and hepatic lipase inversely with calcific atherosclerosis in homozygous familial hypercholesterolemia. Dugi, K.A., Feuerstein, I.M., Hill, S., Shih, J., Santamarina-Fojo, S., Brewer, H.B., Hoeg, J.M. Arterioscler. Thromb. Vasc. Biol. (1997) [Pubmed]
  24. Absence of association between genetic variation in the LIPC gene promoter and plasma lipoproteins in three Canadian populations. Hegele, R.A., Harris, S.B., Brunt, J.H., Young, T.K., Hanley, A.J., Zinman, B., Connelly, P.W. Atherosclerosis (1999) [Pubmed]
  25. Contribution of chromosome 1q21-q23 to familial combined hyperlipidemia in Mexican families. Huertas-Vázquez, A., del Rincón, J.P., Canizales-Quinteros, S., Riba, L., Vega-Hernández, G., Ramírez-Jiménez, S., Aurón-Gómez, M., Gómez-Pérez, F.J., Aguilar-Salinas, C.A., Tusié-Luna, M.T. Ann. Hum. Genet. (2004) [Pubmed]
  26. Interaction of the common apolipoprotein C-III (APOC3 -482C > T) and hepatic lipase (LIPC -514C > T) promoter variants affects glucose tolerance in young adults. European Atherosclerosis Research Study II (EARS-II). Jansen, H., Waterworth, D.M., Nicaud, V., Ehnholm, C., Talmud, P.J. Ann. Hum. Genet. (2001) [Pubmed]
  27. Plasma activities of lipoprotein lipase, hepatic lipase and lecithin: cholesterol acyltransferase in patients considered for parenteral nutrition with fat emulsion. Heller, F., Reynaert, M., Harvengt, C. Am. J. Clin. Nutr. (1985) [Pubmed]
  28. Receptor and non-receptor mediated uptake of chylomicron remnants by the liver. Havel, R.J. Atherosclerosis (1998) [Pubmed]
  29. Maturation of hepatic lipase. Formation of functional enzyme in the endoplasmic reticulum is the rate-limiting step in its secretion. Ben-Zeev, O., Doolittle, M.H. J. Biol. Chem. (2004) [Pubmed]
  30. Cell surface heparan sulfate proteoglycans and lipoprotein metabolism. Kolset, S.O., Salmivirta, M. Cell. Mol. Life Sci. (1999) [Pubmed]
  31. Purification and characterization of lipoprotein lipase and hepatic triglyceride lipase from human postheparin plasma: production of monospecific antibody to the individual lipase. Ikeda, Y., Takagi, A., Yamamoto, A. Biochim. Biophys. Acta (1989) [Pubmed]
  32. Apolipoprotein A-II regulates HDL stability and affects hepatic lipase association and activity. Boucher, J., Ramsamy, T.A., Braschi, S., Sahoo, D., Neville, T.A., Sparks, D.L. J. Lipid Res. (2004) [Pubmed]
  33. Lipoprotein lipase prevents the hepatic lipase-induced reduction in particle size of high density lipoproteins during incubation of human plasma. Newnham, H.H., Hopkins, G.J., Devlin, S., Barter, P.J. Atherosclerosis (1990) [Pubmed]
  34. Apolipoprotein E enhances hepatic lipase-mediated hydrolysis of reconstituted high-density lipoprotein phospholipid and triacylglycerol in an isoform-dependent manner. Hime, N.J., Drew, K.J., Hahn, C., Barter, P.J., Rye, K.A. Biochemistry (2004) [Pubmed]
  35. Evidence that apolipoprotein A-I facilitates hepatic lipase-mediated phospholipid hydrolysis in reconstituted HDL containing apolipoprotein A-II. Hime, N.J., Barter, P.J., Rye, K.A. Biochemistry (2001) [Pubmed]
  36. High density lipoprotein2. Relationship of the plasma levels of this lipoprotein species to its composition, to the magnitude of postprandial lipemia, and to the activities of lipoprotein lipase and hepatic lipase. Patsch, J.R., Prasad, S., Gotto, A.M., Patsch, W. J. Clin. Invest. (1987) [Pubmed]
  37. High-density-lipoprotein metabolism during a very-low-calorie diet. Shoji, T., Nishizawa, Y., Koyama, H., Hagiwara, S., Aratani, H., Sasao, K., Kishimoto, H., Tanishita, H., Morii, H. Am. J. Clin. Nutr. (1992) [Pubmed]
  38. Hydrolysis of phosphatidylcholine by hepatic lipase in discoidal and spheroidal recombinant high-density lipoprotein. Tansey, J.T., Thuren, T.Y., Jerome, W.G., Hantgan, R.R., Grant, K., Waite, M. Biochemistry (1997) [Pubmed]
  39. Hepatic lipase mediates the uptake of chylomicrons and beta-VLDL into cells via the LDL receptor-related protein (LRP). Krapp, A., Ahle, S., Kersting, S., Hua, Y., Kneser, K., Nielsen, M., Gliemann, J., Beisiegel, U. J. Lipid Res. (1996) [Pubmed]
  40. The G-250A promoter polymorphism of the hepatic lipase gene predicts the conversion from impaired glucose tolerance to type 2 diabetes mellitus: the Finnish Diabetes Prevention Study. Todorova, B., Kubaszek, A., Pihlajamäki, J., Lindström, J., Eriksson, J., Valle, T.T., Hämäläinen, H., Ilanne-Parikka, P., Keinänen-Kiukaanniemi, S., Tuomilehto, J., Uusitupa, M., Laakso, M. J. Clin. Endocrinol. Metab. (2004) [Pubmed]
  41. Effects of hormone replacement therapy and hepatic lipase polymorphism on serum lipid profiles in postmenopausal Japanese women. Somekawa, Y., Umeki, H., Kobayashi, K., Tomura, S., Aso, T., Hamaguchi, H. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
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