This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Carr, M. C. Articles by Brunzell, J. D. Search for Related Content PubMed PubMed Citation Articles by Carr, M. C. Articles by Brunzell, J. D. Pubmed/NCBI databases Substance via MeSH

The Contribution of Intraabdominal Fat to Gender Differences in Hepatic Lipase Activity and Low/High Density Lipoprotein Heterogeneity¹

Department of Medicine, Division of Metabolism, Endocrinology and Nutrition (M.C.C., A.Z., J.Q.P., J.D.B.), Division of Medical Genetics (S.S.D.), University of Washington, Seattle, Washington 98195; Department of Preventive Medicine and Biometrics, University of Colorado (J.E.H.), Denver, Colorado 80220; and Department of Medicine, University of Western Australia (P.H.R.B.), Perth, Australia

Address all correspondence and requests for reprints to: Molly C. Carr, M.D., Division of Metabolism, Endocrinology, and Nutrition, Box 356426, University of Washington, Seattle, Washington 98195-6426. E-mail: carr{at}u.washington.edu

Abstract

Hepatic lipase (HL) hydrolyzes triglyceride and phospholipid in low and high density lipoprotein cholesterol (LDL-C and HDL-C, respectively), and elevated HL activity is associated with small, dense atherogenic LDL particles and reduced HDL2-C. Elevated HL activity is associated with increasing age, male gender, high amounts of intraabdominal fat (IAF), and the HL gene (LIPC) promoter polymorphism (C nucleotide at -514). We investigated the mechanisms underlying the difference in HL activity between men (n = 44) and premenopausal women (n = 63).

Men had significantly more IAF (144.5 ± 80.9 vs. 66.5 ± 43.2 cm², respectively; P < 0.001), higher HL activity (220.9 ± 94.7 vs.129.9 ± 53.5 nmol/mL·min; P < 0.001), more dense LDL (Rf, 0.277 ± 0.032 vs. 0.300 ± 0.024; P = 0.01), and less HDL2-C (0.19 ± 0.10 vs. 0.32 ± 0.16 mmol/L; P < 0.001) than women. After adjusting for IAF and the LIPC polymorphism, men continued to have higher (but attenuated) HL activity (194.5 ± 80.4 vs.151.0 ± 45.2, respectively; P = 0.007) and lower HDL2-C (0.23 ± 0.11 vs. 0.29 ± 0.14 mmol/L; P = 0.02) than women. Using multiple regression, HL activity remained independently related to IAF (P < 0.001), gender (P < 0.001), and the LIPC genotype (P < 0.001), with these factors accounting for 50% of the variance in HL activity.

These data suggest that IAF is a major component of the gender difference in HL activity, but other gender-related differences, perhaps sex steroid hormones, also contribute to the higher HL activity seen in men compared with premenopausal women. The higher HL activity in men affects both LDL and HDL heterogeneity and may contribute to the gender difference in cardiovascular risk.

This article has been cited by other articles:

				A. Isaacs, Y. S. Aulchenko, A. Hofman, E. J. G. Sijbrands, F. A. Sayed-Tabatabaei, O. H. Klungel, A.-H. Maitland-van der Zee, B. H. Ch. Stricker, B. A. Oostra, J. C. M. Witteman, et al. Epistatic Effect of Cholesteryl Ester Transfer Protein and Hepatic Lipase on Serum High-Density Lipoprotein Cholesterol Levels J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2680 - 2687. [Abstract] [Full Text] [PDF]

				M.-E. Paradis, K. O. Badellino, D. J. Rader, A. Tchernof, C. Richard, V. Luu-The, Y. Deshaies, J. Bergeron, W. R. Archer, P. Couture, et al. Visceral Adiposity and Endothelial Lipase J. Clin. Endocrinol. Metab., September 1, 2006; 91(9): 3538 - 3543. [Abstract] [Full Text] [PDF]

				N. D. Knuth and J. F. Horowitz The Elevation of Ingested Lipids within Plasma Chylomicrons Is Prolonged in Men Compared with Women J. Nutr., June 1, 2006; 136(6): 1498 - 1503. [Abstract] [Full Text] [PDF]

				P. L. Van, V. K. Bakalov, A. R. Zinn, and C. A. Bondy Maternal X Chromosome, Visceral Adiposity, and Lipid Profile JAMA, March 22, 2006; 295(12): 1373 - 1374. [Full Text] [PDF]

				J. Q. Purnell, L. B. Bland, M. Garzotto, D. Lemmon, E. M. Wersinger, C. W. Ryan, J. D. Brunzell, and T. M. Beer Effects of transdermal estrogen on levels of lipids, lipase activity, and inflammatory markers in men with prostate cancer J. Lipid Res., February 1, 2006; 47(2): 349 - 355. [Abstract] [Full Text] [PDF]

				M. P. Reilly, A. S. Foulkes, M. L. Wolfe, and D. J. Rader Higher order lipase gene association with plasma triglycerides J. Lipid Res., September 1, 2005; 46(9): 1914 - 1922. [Abstract] [Full Text] [PDF]

				C. Zhang, R. Lopez-Ridaura, E. B Rimm, N. Rifai, D. J Hunter, and F. B Hu Interactions between the -514C->T polymorphism of the hepatic lipase gene and lifestyle factors in relation to HDL concentrations among US diabetic men Am. J. Clinical Nutrition, June 1, 2005; 81(6): 1429 - 1435. [Abstract] [Full Text] [PDF]

				N. Yi, S. Chiu, D. B. Allison, J. S. Fisler, and C. H. Warden Epistatic interaction between two nonstructural loci on chromosomes 7 and 3 influences hepatic lipase activity in BSB mice J. Lipid Res., November 1, 2004; 45(11): 2063 - 2070. [Abstract] [Full Text] [PDF]

				A. Isaacs, F. A. Sayed-Tabatabaei, O. T. Njajou, J. C. M. Witteman, and C. M. van Duijn The -514 C->T Hepatic Lipase Promoter Region Polymorphism and Plasma Lipids: A Meta-Analysis J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 3858 - 3863. [Abstract] [Full Text] [PDF]

				D. S. Freedman, J. D. Otvos, E. J. Jeyarajah, I. Shalaurova, L. A. Cupples, H. Parise, R. B. D'Agostino, P. W.F. Wilson, and E. J. Schaefer Sex and Age Differences in Lipoprotein Subclasses Measured by Nuclear Magnetic Resonance Spectroscopy: The Framingham Study Clin. Chem., July 1, 2004; 50(7): 1189 - 1200. [Abstract] [Full Text] [PDF]

				M. C. Carr and J. D. Brunzell Abdominal Obesity and Dyslipidemia in the Metabolic Syndrome: Importance of Type 2 Diabetes and Familial Combined Hyperlipidemia in Coronary Artery Disease Risk J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2601 - 2607. [Abstract] [Full Text] [PDF]

				T. Shimabukuro, M. Sunagawa, and T. Ohta Low-Density Lipoprotein Particle Size and Its Regulatory Factors in School Children J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2923 - 2927. [Abstract] [Full Text] [PDF]

				B. Todorova, A. Kubaszek, J. Pihlajamaki, J. Lindstrom, J. Eriksson, T. T. Valle, H. Hamalainen, P. Ilanne-Parikka, S. Keinanen-Kiukaanniemi, J. Tuomilehto, et al. 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 J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2019 - 2023. [Abstract] [Full Text] [PDF]

				J. S. Volek, M. J. Sharman, A. L. Gomez, C. DiPasquale, M. Roti, A. Pumerantz, and W. J. Kraemer Comparison of a Very Low-Carbohydrate and Low-Fat Diet on Fasting Lipids, LDL Subclasses, Insulin Resistance, and Postprandial Lipemic Responses in Overweight Women J. Am. Coll. Nutr., April 1, 2004; 23(2): 177 - 184. [Abstract] [Full Text] [PDF]

				C.C. Shoulders, E.L. Jones, and R.P. Naoumova Genetics of familial combined hyperlipidemia and risk of coronary heart disease Hum. Mol. Genet., April 1, 2004; 13(90001): R149 - 160. [Abstract] [Full Text] [PDF]

				M. C. Carr, J. D. Brunzell, and S. S. Deeb Ethnic differences in hepatic lipase and HDL in Japanese, black, and white Americans: role of central obesity and LIPC polymorphisms J. Lipid Res., March 1, 2004; 45(3): 466 - 473. [Abstract] [Full Text] [PDF]

				M. A. Austin, K. L. Edwards, S. A. Monks, K. M. Koprowicz, J. D. Brunzell, A. G. Motulsky, M. C. Mahaney, and J. E. Hixson Genome-wide scan for quantitative trait loci influencing LDL size and plasma triglyceride in familial hypertriglyceridemia J. Lipid Res., November 1, 2003; 44(11): 2161 - 2168. [Abstract] [Full Text] [PDF]

				J. S. Volek, M. J. Sharman, A. L. Gomez, T. P. Scheett, and W. J. Kraemer An Isoenergetic Very Low Carbohydrate Diet Improves Serum HDL Cholesterol and Triacylglycerol Concentrations, the Total Cholesterol to HDL Cholesterol Ratio and Postprandial Lipemic Responses Compared with a Low Fat Diet in Normal Weight, Normolipidemic Women J. Nutr., September 1, 2003; 133(9): 2756 - 2761. [Abstract] [Full Text] [PDF]

				S. D. Sibley, J. P. Palmer, I. B. Hirsch, and J. D. Brunzell Visceral Obesity, Hepatic Lipase Activity, and Dyslipidemia in Type 1 Diabetes J. Clin. Endocrinol. Metab., July 1, 2003; 88(7): 3379 - 3384. [Abstract] [Full Text] [PDF]

				S. S. Deeb, A. Zambon, M. C. Carr, A. F. Ayyobi, and J. D. Brunzell Hepatic lipase and dyslipidemia: interactions among genetic variants, obesity, gender, and diet J. Lipid Res., July 1, 2003; 44(7): 1279 - 1286. [Abstract] [Full Text] [PDF]

				S. Rashid, D. K. Trinh, K. D. Uffelman, J. S. Cohn, D. J. Rader, and G. F. Lewis Expression of Human Hepatic Lipase in the Rabbit Model Preferentially Enhances the Clearance of Triglyceride-Enriched Versus Native High-Density Lipoprotein Apolipoprotein A-I Circulation, June 24, 2003; 107(24): 3066 - 3072. [Abstract] [Full Text] [PDF]

				K. L. Herbst, J. K. Amory, J. D. Brunzell, H. A. Chansky, and W. J. Bremner Testosterone administration to men increases hepatic lipase activity and decreases HDL and LDL size in 3 wk Am J Physiol Endocrinol Metab, June 1, 2003; 284(6): E1112 - E1118. [Abstract] [Full Text] [PDF]

				I. I.L. Berk-Planken, N. Hoogerbrugge, R. P. Stolk, A. H. Bootsma, and H. Jansen Atorvastatin Dose-Dependently Decreases Hepatic Lipase Activity in Type 2 Diabetes: Effect of sex and the LIPC promoter variant Diabetes Care, February 1, 2003; 26(2): 427 - 432. [Abstract] [Full Text] [PDF]

				D. J. Nieves, M. Cnop, B. Retzlaff, C. E. Walden, J. D. Brunzell, R. H. Knopp, and S. E. Kahn The Atherogenic Lipoprotein Profile Associated With Obesity and Insulin Resistance Is Largely Attributable to Intra-Abdominal Fat Diabetes, January 1, 2003; 52(1): 172 - 179. [Abstract] [Full Text] [PDF]

				Y. Somekawa, H. Umeki, K. Kobayashi, S. Tomura, T. Aso, and H. Hamaguchi Effects of Hormone Replacement Therapy and Hepatic Lipase Polymorphism on Serum Lipid Profiles in Postmenopausal Japanese Women J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4766 - 4770. [Abstract] [Full Text] [PDF]

				H. Jansen, A. J. M. Verhoeven, and E. J. G. Sijbrands Hepatic lipase: a pro- or anti-atherogenic protein? J. Lipid Res., September 1, 2002; 43(9): 1352 - 1362. [Abstract] [Full Text] [PDF]

				M.C. Carr, A.F. Ayyobi, S.J. Murdoch, S.S. Deeb, and J.D. Brunzell Contribution of Hepatic Lipase, Lipoprotein Lipase, and Cholesteryl Ester Transfer Protein to LDL and HDL Heterogeneity in Healthy Women Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 667 - 673. [Abstract] [Full Text] [PDF]

				M.C. Carr, A.F. Ayyobi, S.J. Murdoch, S.S. Deeb, and J.D. Brunzell Contribution of Hepatic Lipase, Lipoprotein Lipase, and Cholesteryl Ester Transfer Protein to LDL and HDL Heterogeneity in Healthy Women Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 667 - 673. [Abstract] [Full Text] [PDF]