Hepatic lipase and dyslipidemia: interactions among genetic variants, obesity, gender, and diet.

Hepatic lipase (HL) plays a central role in LDL and HDL remodeling. High HL activity is associated with small, dense LDL particles and with reduced HDL2 cholesterol levels. HL activity is determined by an HL gene promoter polymorphism, by gender (lower in premenopausal women), and by visceral obesity with insulin resistance. The activity is affected by dietary fat intake and selected medications. There is evidence for an interaction of the HL promoter polymorphism with visceral obesity, dietary fat intake, and with lipid-lowering medications in determining the level of HL activity. The dyslipidemia with high HL activity is a potentially proatherogenic lipoprotein profile in the metabolic syndrome, in Type 2 diabetes, and in familial combined hyperlipidemia.

[1]  P. Wilson,et al.  Dietary Fat Intake Determines the Effect of a Common Polymorphism in the Hepatic Lipase Gene Promoter on High-Density Lipoprotein Metabolism: Evidence of a Strong Dose Effect in This Gene-Nutrient Interaction in the Framingham Study , 2002, Circulation.

[2]  J. Ordóñez‐Llanos,et al.  Mechanisms of HDL deficiency in mice overexpressing human apoA-II DOI 10.1194/jlr.M200081-JLR200 , 2002, Journal of Lipid Research.

[3]  T. Aso,et al.  Effects of hormone replacement therapy and hepatic lipase polymorphism on serum lipid profiles in postmenopausal Japanese women. , 2002, Journal of Clinical Endocrinology and Metabolism.

[4]  E. Sijbrands,et al.  Hepatic lipase: a pro- or anti-atherogenic protein? , 2002, Journal of lipid research.

[5]  L. Martinez,et al.  Hepatic lipase: structure/function relationship, synthesis, and regulation. , 2002, Journal of lipid research.

[6]  P. Eacho,et al.  Estrogen receptor-mediated repression of human hepatic lipase gene transcription. , 2002, Journal of lipid research.

[7]  M. Krieger,et al.  Scavenger receptor class B type I is a multiligand HDL receptor that influences diverse physiologic systems. , 2001, The Journal of clinical investigation.

[8]  J. Hokanson,et al.  The contribution of intraabdominal fat to gender differences in hepatic lipase activity and low/high density lipoprotein heterogeneity. , 2001, The Journal of clinical endocrinology and metabolism.

[9]  A. Verhoeven,et al.  Hepatic lipase promoter activity is reduced by the C-480T and G-216A substitutions present in the common LIPC gene variant, and is increased by Upstream Stimulatory Factor. , 2001, Atherosclerosis.

[10]  S. Juo,et al.  Promoter polymorphisms of hepatic lipase gene influence HDL(2) but not HDL(3) in African American men: CARDIA study. , 2001, Journal of lipid research.

[11]  N. Siseles,et al.  Higher values of hepatic lipase activity in postmenopause: relationship with atherogenic intermediate density and low density lipoproteins , 2001, Menopause.

[12]  S. Deeb,et al.  In vivo evidence of a role for hepatic lipase in human apoB-containing lipoprotein metabolism, independent of its lipolytic activity. , 2000, Journal of lipid research.

[13]  C. Bouchard,et al.  Race, visceral adipose tissue, plasma lipids, and lipoprotein lipase activity in men and women: the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) family study. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[14]  J. Hokanson,et al.  Common Hepatic Lipase Gene Promoter Variant Determines Clinical Response to Intensive Lipid-Lowering Treatment , 2000, Circulation.

[15]  T. Thuren.  Hepatic lipase and HDL metabolism. , 2000, Current opinion in lipidology.

[16]  R. Schwartz,et al.  Effect of weight loss with reduction of intra-abdominal fat on lipid metabolism in older men. , 2000, The Journal of clinical endocrinology and metabolism.

[17]  R. F. Hoyt,et al.  In vivo evidence for both lipolytic and nonlipolytic function of hepatic lipase in the metabolism of HDL. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[18]  M. Lefevre,et al.  HDL-subpopulation patterns in response to reductions in dietary total and saturated fat intakes in healthy subjects. , 1999, The American journal of clinical nutrition.

[19]  J. Hokanson,et al.  A hepatic lipase gene promoter polymorphism attenuates the increase in hepatic lipase activity with increasing intra-abdominal fat in women. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[20]  B. Howard,et al.  LDL size in African Americans, Hispanics, and non-Hispanic whites : the insulin resistance atherosclerosis study. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[21]  S. Grundy,et al.  Hepatic lipase: new insights from genetic and metabolic studies. , 1999, Current opinion in lipidology.

[22]  C. Haudenschild,et al.  The role of hepatic lipase in lipoprotein metabolism and atherosclerosis. , 1999, Current opinion in lipidology.

[23]  J. Hokanson,et al.  Evidence for a new pathophysiological mechanism for coronary artery disease regression: hepatic lipase-mediated changes in LDL density. , 1999, Circulation.

[24]  J. Hokanson,et al.  Dyslipidemia of central obesity and insulin resistance. , 1999, Diabetes Care.

[25]  A. Wakatsuki,et al.  Small low-density lipoprotein particles in women with natural or surgically induced menopause. , 1999, Obstetrics and gynecology.

[26]  J. Hokanson,et al.  Common variants in the promoter of the hepatic lipase gene are associated with lower levels of hepatic lipase activity, buoyant LDL, and higher HDL2 cholesterol. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[27]  R. Krauss,et al.  Change in dietary saturated fat intake is correlated with change in mass of large low-density-lipoprotein particles in men. , 1998, The American journal of clinical nutrition.

[28]  M. Taskinen,et al.  Association of variation in hepatic lipase activity with promoter variation in the hepatic lipase gene. The LOCAT Study Invsestigators. , 1998, The Journal of clinical investigation.

[29]  S. Grundy,et al.  Effect of statins on metabolism of apo-B-containing lipoproteins in hypertriglyceridemic men. , 1998, The American journal of cardiology.

[30]  R. Mahley,et al.  Overexpression of Hepatic Lipase in Transgenic Mice Decreases Apolipoprotein B-containing and High Density Lipoproteins , 1998, The Journal of Biological Chemistry.

[31]  R. Mahley,et al.  Heparan Sulfate Proteoglycans Participate in Hepatic Lipaseand Apolipoprotein E-mediated Binding and Uptake of Plasma Lipoproteins, Including High Density Lipoproteins* , 1997, The Journal of Biological Chemistry.

[32]  J. Jukema,et al.  Common C-to-T substitution at position -480 of the hepatic lipase promoter associated with a lowered lipase activity in coronary artery disease patients. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[33]  L. Tiret,et al.  Hepatic lipase gene polymorphisms influence plasma HDL levels. Results from Finnish EARS participants. European Atherosclerosis Research Study. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[34]  P. Connelly,et al.  Uptake of hypertriglyceridemic very low density lipoproteins and their remnants by HepG2 cells: the role of lipoprotein lipase, hepatic triglyceride lipase, and cell surface proteoglycans. , 1997, Journal of lipid research.

[35]  S. Yokoyama,et al.  Apolipoprotein-mediated removal of cellular cholesterol and phospholipids. , 1996, Journal of lipid research.

[36]  A. Gotto,et al.  Apolipoprotein A-II influences the substrate properties of human HDL2 and HDL3 for hepatic lipase. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[37]  U. Beisiegel,et al.  Hepatic lipase mediates the uptake of chylomicrons and beta-VLDL into cells via the LDL receptor-related protein (LRP). , 1996, Journal of lipid research.

[38]  E. Brinton.  Oral estrogen replacement therapy in postmenopausal women selectively raises levels and production rates of lipoprotein A-I and lowers hepatic lipase activity without lowering the fractional catabolic rate. , 1996, Arteriosclerosis, thrombosis, and vascular biology.

[39]  M. A. Lasunción,et al.  Longitudinal study on lipoprotein profile, high density lipoprotein subclass, and postheparin lipases during gestation in women. , 1996, Journal of lipid research.

[40]  C. Packard,et al.  Relations between plasma lipids and postheparin plasma lipases and VLDL and LDL subfraction patterns in normolipemic men and women. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[41]  D. Applebaum-Bowden,et al.  Lipases and lecithin: cholesterol acyltransferase in the control of lipoprotein metabolism , 1995, Current opinion in lipidology.

[42]  C. Bouchard,et al.  Does lipoprotein or hepatic lipase activity explain the protective lipoprotein profile of premenopausal women? , 1995, Metabolism: clinical and experimental.

[43]  R. Krauss,et al.  Associations of hepatic and lipoprotein lipase activities with changes in dietary composition and low density lipoprotein subclasses. , 1995, Journal of lipid research.

[44]  C. Packard,et al.  Determinants of LDL subfraction distribution and concentrations in young normolipidemic subjects. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[45]  A. van Tol,et al.  Hepatic lipase and lipoprotein lipase are not major determinants of the low density lipoprotein subclass pattern in human subjects with coronary heart disease. , 1994, Atherosclerosis.

[46]  A Tremblay,et al.  Sex differences in the relation of visceral adipose tissue accumulation to total body fatness. , 1993, The American journal of clinical nutrition.

[47]  S. Grundy,et al.  Activities of lipoprotein lipase and hepatic triglyceride lipase in postheparin plasma of patients with low concentrations of HDL cholesterol. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[48]  R. Hegele,et al.  Hepatic lipase deficiency. Clinical, biochemical, and molecular genetic characteristics. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[49]  G. Mcclearn,et al.  Genetic and environmental influences on serum lipid levels in twins. , 1993, The New England journal of medicine.

[50]  S. Martino,et al.  Dietary and anthropometric determinants of plasma lipoproteins during a long-term low-fat diet in healthy women. , 1993, The American journal of clinical nutrition.

[51]  J. Hokanson,et al.  Effect of hepatic lipase on LDL in normal men and those with coronary artery disease. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[52]  W. Hazzard,et al.  A dose-response relationship between sex hormone-induced change in hepatic triglyceride lipase and high-density lipoprotein cholesterol in postmenopausal women. , 1991, Metabolism: clinical and experimental.

[53]  B. G. Brown,et al.  Altered particle size distribution of apolipoprotein A-I-containing lipoproteins in subjects with coronary artery disease. , 1991, Journal of lipid research.

[54]  C. Bouchard,et al.  Role of hepatic-triglyceride lipase activity in the association between intra-abdominal fat and plasma HDL cholesterol in obese women. , 1989, Arteriosclerosis.

[55]  J. Hokanson,et al.  Large Buoyant LDL‐like Particles in Hepatic Lipase Deficiency , 1989, Arteriosclerosis.

[56]  W C Willett,et al.  Low-density lipoprotein subclass patterns and risk of myocardial infarction. , 1988, JAMA.

[57]  M. Taskinen,et al.  Effects of endogenous sex steroids on serum lipoproteins and postheparin plasma lipolytic enzymes. , 1988, The Journal of clinical endocrinology and metabolism.

[58]  P. Wilson,et al.  Effect of Gender, Age, and Lipid Status on Low Density Lipoprotein Su bf raction Distribution: Results from the Framingham Offspring Study , 1987, Arteriosclerosis.

[59]  E. Nikkilä,et al.  Regulation of hepatic lipase and serum lipoproteins by sex steroids. , 1987, American heart journal.

[60]  U. Stenman,et al.  Variation of postheparin plasma hepatic lipase by menstrual cycle. , 1986, Metabolism: clinical and experimental.

[61]  M. Phillips,et al.  Mechanism of the hepatic lipase induced accumulation of high-density lipoprotein cholesterol by cells in culture. , 1985, Biochemistry.

[62]  E. Nikkilä,et al.  Effects of two progestins with different androgenic properties on hepatic endothelial lipase and high density lipoprotein2. , 1985, Atherosclerosis.

[63]  W. Hazzard,et al.  Reduction in high density lipoproteins by anabolic steroid (stanozolol) therapy for postmenopausal osteoporosis. , 1982, Metabolism: clinical and experimental.

[64]  E. Nikkilä,et al.  High density lipoprotein-2 and hepatic lipase: reciprocal changes produced by estrogen and norgestrel. , 1982, The Journal of clinical endocrinology and metabolism.

[65]  E. Nikkilä,et al.  Effects of oestradiol and levonorgestrel on lipoprotein lipids and postheparin plasma lipase activities in normolipoproteinaemic women. , 1982, Acta endocrinologica.

[66]  E. Nikkilä,et al.  Evidence for the role of hepatic endothelial lipase in the metabolism of plasma high density lipoprotein2 in man. , 1980, Atherosclerosis.

[67]  D. Jacobs,et al.  Lipoprotein‐Cholesterol Distributions in Selected North American Populations: The Lipid Research Clinics Program Prevalence Study , 1980, Circulation.

[68]  E. Vartiainen,et al.  Natural oestrogen as an effective treatment for type-II hyperlipoproteinaemia in postmenopausal women. , 1979, Lancet.

[69]  E. Vartiainen,et al.  NATURAL ŒSTROGEN AS AN EFFECTIVE TREATMENT FOR TYPE-II HYPERLIPOPROTEINÆMIA IN POSTMENOPAUSAL WOMEN , 1978, The Lancet.

[70]  A. Goldberg,et al.  Effect of estrogen on post-heparin lipolytic activity. Selective decline in hepatic triglyceride lipase. , 1977, The Journal of clinical investigation.

[71]  J. Huttunen,et al.  Post-heparin plasma lipoprotein lipase and hepatic lipase in normal subjects and in patients with hypertriglyceridaemia: correlations to sex, age and various parameters of triglyceride metabolism. , 1976, Clinical science and molecular medicine.

[72]  J. Huttunen,et al.  Effect of oxandrolone treatment on the activity of lipoprotein lipase, hepatic lipase and phospholipase A1 of human postheparin plasma. , 1975, The New England journal of medicine.

[73]  L. Carlson,et al.  Quantitative and qualitative serum lipoprotein analysis. Part 2. Studies in male survivors of myocardial infarction. , 1975, Atherosclerosis.

[74]  L. Carlson,et al.  Quantitative and qualitative serum lipoprotein analysis. Part 1. Studies in healthy men and women. , 1975, Atherosclerosis.

[75]  S. Deeb,et al.  The C-514T polymorphism in the human hepatic lipase gene promoter diminishes its activity. , 2000, Journal of lipid research.

[76]  H. Brewer,et al.  Hepatic lipase promotes the selective uptake of high density lipoprotein-cholesteryl esters via the scavenger receptor B 1 , 1999 .

[77]  S. Grundy,et al.  Hepatic lipase activity is lower in African American men than in white American men: effects of 5' flanking polymorphism in the hepatic lipase gene (LIPC). , 1998, Journal of lipid research.

[78]  R. Hegele,et al.  Hepatic lipase deficiency. , 1998, Critical reviews in clinical laboratory sciences.

[79]  U. Garbin,et al.  High-density lipoprotein cholesterol concentrations and postheparin hepatic and lipoprotein lipases in obesity: relationships with plasma insulin levels. , 1993, Annals of nutrition & metabolism.

[80]  J. RMcNamara,et al.  Effect of gender, age, and lipid status on low density lipoprotein subfraction distribution. Results from the Framingham Offspring Study. , 1987 .