help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Carr, M. C.
Right arrow Articles by Brunzell, J. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Carr, M. C.
Right arrow Articles by Brunzell, J. D.
The Journal of Clinical Endocrinology & Metabolism Vol. 86, No. 6 2831-2837
Copyright © 2001 by The Endocrine Society

Other Original Studies

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

Molly C. Carr, John E. Hokanson, Alberto Zambon, Samir S. Deeb, P. Hugh R. Barrett, Jonathan Q. Purnell and John D. Brunzell

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.

HEPATIC LIPASE (HL) is a lipolytic enzyme that hydrolyzes triglyceride (TG) and phospholipid in low and high density lipoprotein cholesterol (LDL-C and HDL-C, respectively) (1, 2) and contributes to determining the lipoprotein particle size and density (3) of each. The higher the HL activity, the more TG and phospholipid hydrolyzed, resulting in smaller, denser LDL (4) and HDL particles that are thought to be more atherogenic (5, 6).

HL activity appears to be regulated by several factors, including 1) HL gene (LIPC) promoter polymorphism (7, 8); 2) obesity, specifically intraabdominal fat (IAF) (9); 3) gender (10, 11); 4) sex steroid hormones (12, 13); and 5) age (10, 14). Four polymorphisms (G to A substitution at position -250, C to T at -514, T to C at -710, and A to G at -763) (15) have been identified in the promoter region of the LIPC gene and account for 20% of the variance in HL activity in Caucasians (8, 16). These polymorphisms appear to be in complete linkage disequilibrium in Caucasian populations and together define two haplotypes. The frequency of the less common haplotype ranges from 0.15 (15) to 0.21 (8) in Caucasian populations and from 0.45 (8) to 0.53 (7) in African-Americans (-250 G to A) and is 0.47 in Japanese-Americans (-250 G to A) (8). With high levels of intraabdominal obesity, increased HL activity in postheparin plasma is seen, which leads to smaller and denser LDL particles (17, 18). Weight loss leads to a reduction in HL activity (19) related specifically to the loss of IAF (20).

Men have twice as high HL activity as women (21), and gender alone has been shown to account for 28.5% of the variability in HL activity (22). HL activity is inversely associated with endogenous estrogen levels (23), and it is higher in postmenopausal compared with premenopausal women (24). HL activity decreases significantly with oral estrogens (12, 25) and increases 3-fold with androgenic steroids (13, 26).

The risk of CAD is lower in middle-aged women than men, but increases with estrogen deficiency (27). Premenopausal women have a less atherogenic lipid profile than men due to higher HDL-C (28), higher levels of large, buoyant HDL2-C (21), and lower triglyceride levels (29). LDL-C levels are not consistently lower than those in age-matched men (29), but women are less likely than men to have small, dense LDL particles (30), which are more atherogenic than large, buoyant LDL particles (5). The temporal separation in the onset of CAD risk between sexes may be partially explained by the gender differences in lipoprotein profile and may be related in part to differences in HL activity. These differences in HL activity have led some to hypothesize that HL activity is a major determinant of the more atherogenic lipoprotein profile in men compared with women (31, 32).

The higher amount of IAF in men (33) may account for a substantial part of the gender dimorphism in HL activity. The current study was designed to understand the effect of gender on HL activity while accounting for factors known to influence HL activity. The purpose of the study was to determine what proportion of the gender difference in HL activity between men and women could be attributed to gender differences in visceral fat.

Subjects and Methods

Research subjects

Forty-four healthy men, aged 21–75 yr, and 63 healthy, premenopausal women, aged 21–54 yr, were studied. Fifty premenopausal women were participating in a community-based study (34), and the additional 13 premenopausal women were controls for a study of weight loss and were taking no estrogen. The women did not have blood drawn on coordinated days of their menstrual cycles. The premenopausal state was defined as having had menstrual flow in the previous 6 months. Forty-four men were selected by advertisement as controls or subjects for a weight loss study in healthy men (20).

Subjects were excluded from the study if they had a body mass index (BMI) greater than 40 kg/m2 or TG or LDL-C levels greater than the 95th percentile for age (35). None of the subjects were taking any lipid-altering medications, including ß-blockers or estrogen. The subjects were nonsmokers and had no evidence of liver disease. The human subjects review committee of the University of Washington approved the study protocol, and informed consent was obtained from all participants.

Blood collection

Blood was collected in 0.1% ethylenediamine tetraacetate after a 12- to 16-h overnight fast for DNA isolation, lipoprotein measurements, and density gradient ultracentrifugation (DGUC). A heparin bolus of 60 U/kg was given, and blood was collected after 10 min in lithium heparin tubes for the measurement of lipase activity. Blood was immediately centrifuged at 4 C at 3000 rpm for 15 min. Lipase activities were obtained on postheparin plasma that had been immediately frozen and stored at -70 C.

Lipoprotein measures

Plasma total cholesterol, HDL-C, HDL2-C, TG, and apolipoprotein B (apo B) were quantitated by published techniques (36) using an Abbott Spectrum Bichromatic Analyzer (Irving, TX) at the Northwest Lipid Research Laboratory (Seattle, WA). LDL-C was calculated according to Friedewald’s formula. Lipid measurements were made within 2 days on fresh plasma that had been stored at 4 C.

Postheparin lipase activity

The total lipolytic activity was measured in plasma after heparin bolus as previously described (37). Glycerol tri[1-14C]oleate (Amersham Pharmacia Biotech, Arlington Heights, IL)-labeled TG, lecithin, and albumin (Sigma, St. Louis, MO) were incubated with postheparin plasma for 60 min at 37 C, and the liberated 14C-labeled free fatty acids were then extracted and counted. Lipoprotein lipase (LpL) activity was calculated as the lipolytic activity removed from plasma by incubation with a specific monoclonal antibody against LpL (5D2), and HL activity was determined as the activity remaining after incubation with the LpL antibody. Enzyme activity is expressed as nanomoles of free fatty acid released per min/mL plasma at 37 C. For each assay, a bovine milk LpL standard was used to correct for interassay variation, and a human postheparin plasma standard was included to monitor interassay variation. The interassay coefficient of variation of hepatic lipase is 4.9%.

Density gradient ultracentrifugation

A discontinuous salt density gradient was created in an ultracentrifuge tube using a modification (38) of a previous method (39). Samples were centrifuged at 65,000 rpm for 70 min (total {omega}t2 = 1.95 x 1011) at 10 C in a VTi 65.1 (Beckman Coulter, Inc., Palo Alto, CA) vertical rotor. Thirty-eight 0.45-mL fractions were then collected from the bottom of the centrifuge tube, and cholesterol was measured in each fraction. The relative flotation rate (Rf), which characterizes LDL peak buoyancy, was obtained by dividing the fraction number containing the LDL-C peak by the total number of fractions collected. The coefficient of variation of the Rf value obtained by replicate analysis was 3.6% as described previously (40).

DNA isolation and analysis

DNA was extracted from leukocytes of 10 mL freshly drawn blood by the salting-out method described by Miller et al. (41). The genotype at nucleotide position -514 was determined by PCR amplification as described previously (8).

Abdominal adipose content

Visceral adiposity was measured by computed tomography (CT) scan (GE Highspeed Advantage, Milwaukee, WI). A single image was obtained by CT scan on inspiration at the level of the umbilicus. The CT image was analyzed for cross-sectional area of fat using a density contour program available with the standard GE computer software (GE, Milwaukee, WI) as described previously (42). A single blinded observer made all of the CT measurements of intraabdominal and sc fat, with intraobserver variability upon reading the same CT scan less than 1.5%.

Statistical methods

Statistical analyses were performed using SigmaStat, version 2.0, and SigmaPlot, version 6.0 (Jandel Scientific, San Ramon, CA). Comparisons between sexes and genotypes were performed using unpaired t tests and Mann-Whitney rank-sum test. HL activity, lipid measures, and BMI were adjusted linearly for the effect of log IAF and the LIPC genotype. The relationship of HL activity to gender, IAF, and LIPC genotype was obtained by multiple linear regression. The independent contribution of each factor (gender, IAF, and LIPC) to HL activity was obtained by the partial correlation coefficient (percent variance accounted for by; SS marg/total SS). The total variance explained by the combined effect of all factors on HL activity was assessed by P values and adjusted R2. IAF was log transformed for multiple regression and linear adjustment, as the relationship between IAF and HL is curvilinear, as previously described (18). Multiple linear regression analyses were performed to assess the relationship of LDL peak particle density (LDL-Rf), HDL2-C, and HDL3-C to gender, HL activity, log IAF, and log TG. Hardy-Weinberg equilibrium was tested using {chi}2 analysis. The significance level was set at {alpha} = 0.05. The SAAM II program (SAAM Institute, Seattle, WA) was used for the curvilinear modeling the HL and IAF data. A rectangular hyperbola model provided the best description of the data, as assessed using the parsimony criteria.

Results

Characteristics of the cohort

Measures of truncal obesity were significantly higher in men than women (IAF, P < 0.001; waist/hip raio, P < 0.001), whereas the amount of abdominal sc fat was not different between the sexes (P = 0.89; Table 1Go). Men had more than twice the amount of IAF as women (144.5 ± 80.9 vs. 66.5 ± 43.2 cm2, respectively; P < 0.001), with IAF ranging from 6.8–272.6 cm2 in men and from 10.5–183.5 cm2 in women. Men had significantly higher age (P = 0.009) and BMI (P = 0.007) than the women.


View this table:
[in this window]
[in a new window]
  		Table 1. Characteristics of entire cohort (all genotypes)

 
Men had significantly higher HL activity than women (P < 0.001), but there was no significant gender difference in LpL activity (P = 0.83). Men had significantly higher TG (P = 0.002) and apo B (P = 0.015) than women. Women had significantly higher HDL-C (P < 0.001), HDL2-C (P < 0.001), and HDL3-C (P < 0.001) than men, whereas plasma LDL-C and total cholesterol were similar in the two groups. LDL-Rf was significantly lower (more dense) in men than in women (P = 0.013).

Effects of gender on HL activity and lipids, independent of LIPC genotype and IAF

Before statistical adjustment, HL was 41% higher in men than women (P < 0.001). After adjustment for both IAF and LIPC genotype, HL remained significantly higher in the men than the women (P = 0.007), but the gender dimorphism was reduced to 22% (Fig. 1Go and Table 2Go). After this adjustment the apo A-containing particles (HDL-C, HDL2-C, and HDL3-C) remained significantly different in men and women (P = 0.002, P = 0.02, and P < 0.001, respectively), whereas the gender dimorphism in TG, apo B, and LDL-Rf was erased (P = 0.62, P = 0.48, and P = 0.18, respectively; Table 2Go). After adjustment, a significant difference in total cholesterol between men and women (P = 0.02) was seen and was attributed entirely to the differences in apo A-containing HDL particles. After adjustment for LIPC genotype and IAF, the gender difference in BMI was erased (27.1 ± 3.5 vs. 28.2 ± 3.7 kg/m2; P = 0.32).



View larger version (20K):
[in this window]
[in a new window]
  		Figure 1. HL activity in men and women before and after adjustment for IAF and LIPC promoter genotype.

 

View this table:
[in this window]
[in a new window]
  		Table 2. Comparison of men and women after adjustment for IAF and LIPC genotype

 
Multiple linear analysis revealed that gender (P < 0.001) was highly significantly related to HL activity (Table 3Go). When IAF and LIPC genotype were included in the same model, gender (P < 0.001), IAF (P < 0.001), and the LIPC genotype (P < 0.001) were all independently related to HL activity. The combined effect of these three factors accounts for 50% of the variance in HL activity (adjusted r2 = 0.499). The effects of each individual factor (IAF, gender, and LIPC genotype) on the variance in HL activity were 14.4%, 14.2%, and 10.9%, respectively, independent of each other. Age was related to HL activity with linear regression (r = 0.30; P = 0.002), but was not significantly related to HL activity in multivariate analyses with gender alone or gender, IAF, and LIPC genotype. Multiple linear regression analysis also revealed that IAF (P < 0.001) was significantly related to HL activity, whereas BMI was not related to HL activity (P = 0.99).


View this table:
[in this window]
[in a new window]
  		Table 3. Relationship of HL activity with gender, IAF, and LIPC

 
Multiple regression analysis revealed that LDL buoyancy (LDL-Rf) was significantly independently related to HL activity (P = 0.006) and TG (P < 0.001), but not gender (P = 0.15) or IAF (P = 0.068), and these factors accounted for 46% of the total variance in LDL-Rf (r2 = 0.464; Table 4Go). Although gender and IAF did not appear to be related to LDL-Rf in multivariate analysis, they were related to LDL-Rf in linear regression (gender: r = 0.21; P = 0.03; IAF: r = 0.53; P < 0.001). In a similar model, multiple regression revealed that HDL2-C was significantly related to HL activity (P = 0.005) and TG (P = 0.046), but was not independently related to gender (P = 0.08) or IAF (P = 0.56), and these factors accounted for 33% of the total variance in HDL2-C (r2 = 0.328).


View this table:
[in this window]
[in a new window]
  		Table 4. Effect of gender, HL activity, IAF, and TG on LDL/HDL heterogeneity

 
Effect of LIPC genotype on HL activity in men and women

To control for the effect of the LIPC genotype on HL activity, men and women of the same LIPC promoter genotype were compared. Among the subjects with the CC genotype, men had 46% higher HL activity than women (260.5 ± 87.7 vs. 140.7 ± 58.5 nmol/mL·min, respectively; P < 0.001; Table 5Go). Males with the CT/TT genotypes combined had 40% higher levels of HL activity than females with CT/TT genotypes (181.2 ± 85.9 vs. 108.3 ± 33.4 nmol/mL·min, respectively; P < 0.001).


View this table:
[in this window]
[in a new window]
  		Table 5. Comparison of men and women with CC (A) and CT/TT (B) Genotypes

 
Women with the CC genotype had significantly higher levels of HL activity than those with the CT/TT genotypes combined (CC, 140.7 ± 58.5; CT/TT, 108.3 ± 33.4 nmol/mL·min; P = 0.022). There was no significant difference in the amount of IAF between these two groups of women that could account for the difference in HL activity (CC, 63.4 ± 41.0; CT/TT, 72.7 ± 47.5 cm2; P = 0.43). As in the women, males (Fig. 2Go) with the CC genotype had significantly higher HL activity than males with the CT/TT genotypes combined (CC, 260.5 ± 87.7; CT/TT, 181.2 ± 85.9 nmol/mL·min; P = 0.004). There was no significant difference in IAF between these two groups of men (CC, 145.1 ± 84.4; CT/TT, 143.8 ± 79.1 cm2; P = 0.96). Allele frequencies between men and women were not different (P = 0.21). The population sample studied was in Hardy-Weinberg equilibrium ({chi}2 = 0.2; P = 0.91).



View larger version (18K):
[in this window]
[in a new window]
  		Figure 2. HL activity in men and women separated by LIPC promoter genotype.

 
Nonlinear relationship of HL and IAF

Within the CC genotype, there was a significant curvilinear relationship between HL activity and IAF in men (P < 0.05) and women (P < 0.05). HL activity increases with IAF until an apparent maximum is reached. This apparent maximum depends on the LIPC genotype. Using a curvilinear model based on a rectangular hyperbola (see Materials and Methods), one can calculate a maximal level for HL activity within each gender. The maximal level of HL activity in men with the CC genotype was significantly higher than that in women with the CC genotype (296.3 vs. 222.7 nmol/mL·min, respectively), with a 95% confidence interval for the apparent maximum in males of 283.0–309.5 nmol/mL·min and for the apparent maximum in females of 196.7–248.7 nmol/mL·min (P < 0.001).

Discussion

In this study we have compared the differences in HL activity between men and premenopausal women while controlling for the effects of the HL gene promoter polymorphism and IAF, both known to affect HL activity. After controlling for the effect of IAF and the LIPC genotype on HL activity, men continued to have significantly higher HL activity than women, but the difference was reduced by approximately 50%. These results suggest that IAF accounts for a portion of the gender difference in HL activity, but there is still a residual difference in HL activity not accounted for by visceral obesity or the LIPC genotype.

This residual effect of gender on HL activity may represent gender differences in sex steroid hormones (43) that act to influence HL activity. HL activity has been shown to be highly sensitive to changes in both exogenous (25) and endogenous sex steroids (23, 44). HL activity falls significantly in women during the luteal phase of the menstrual cycle when endogenous estradiol levels are highest (23). A study of endogenous testosterone production in prepubescent boys showed a rise in androgen levels associated with a significant increase in HL activity (44).

Gender, IAF, and the LIPC polymorphism each contributed independently to the variance in HL activity. Fifty percent of the total variance in HL activity is accounted for by the combined effect of visceral obesity (14.4%), gender (14.2%), and the HL gene promoter polymorphism (10.9%). Although IAF is related to gender, they each appear to have independent effects on HL activity. Age has been reported to be associated with HL activity (10, 14), but this relationship does not appear to be independent of visceral adiposity or gender. The remaining 50% of the variance in HL activity was unaccounted for, but may represent in part methodological errors in measuring HL activity and IAF.

The effect of the LIPC promoter genotype on HL activity appears to be the same in men and women. Males and females with the CC genotype had significantly higher levels of HL activity than subjects with the T allele for the same amount of visceral adiposity. As has been shown previously (7, 8, 16), the presence of the LIPC-514T allele limits HL activity and confers benefit to the lipid profile. Recent transfection studies have shown that the T allele diminishes transcriptional activity by approximately 30% (45). The degree to which the presence of the T allele limits the increase in HL activity, as a function of IAF content, appears to be the same in men and women in this cohort. As we have shown previously in women (18), there is a complex relationship between HL activity and IAF. As the amount of visceral adiposity increases, HL activity increases until an apparent maximum is reached in both sexes. We found that the curvilinear relationships fit the data better. A maximal level of HL activity is approached as IAF increases, and the maximum HL activity is 33% higher in men than in women with the same LIPC genotype.

The sexual differences in plasma lipids are not solely accounted for by the differences in IAF and LIPC genotype. In agreement with previous studies, before statistical adjustment premenopausal women had higher HDL-C, HDL2-C, and HDL3-C and lower HL activity, TG, and apo B than men (46). After adjustment for the effect of IAF and HL gene promoter genotype on plasma lipids, HDL-C, HDL2-C, and HDL3-C remained significantly different between men and women. Despres et al. have shown that adjustment for both LpL and HL activities failed to eliminate the differences in plasma lipids between men and women (47). This residual higher HDL-C seen in women after adjustment may be related to the direct effect of estrogen on apo A-1 production (48, 49).

After adjustment of lipoprotein measures for IAF and LIPC promoter genotype, the gender differences in TG and LDL-C were erased. Other studies have shown that controlling for waist circumference also reduces the male/female differences in TG and apo B (50, 51). Central obesity appears to lead to insulin resistance and an increase in TG, small, dense LDL particles, and a decrease in HDL2-C (52). In previous studies a causal relationship among IAF, HL activity, and LDL size and density has been established (20) (Fig. 3Go). In the present study when the gender effects on LDL-Rf were adjusted for IAF, the gender differences in LDL-Rf were gone. This may imply that HL activity has no effect on the gender difference in LDL-Rf after accounting for IAF. However, we have shown that both HL activity and TG are significantly independently related to LDL-Rf, which may reflect the combined actions of HL activity (hydrolyzing TG and phospholipid) and cholesteryl ester transfer protein (CETP; transferring core lipids) in determining the core composition of LDL particles. One explanation (for the loss of gender difference in LDL-Rf after adjustment for IAF) is that the women with large, buoyant LDL cannot develop more buoyant LDL. This result has been reported twice before. Individuals with small, dense LDL at baseline developed large, buoyant LDL with weight loss (20) and aggressive lipid lowering (53), whereas those with large, buoyant LDL at baseline did not improve despite a reduction in HL activity. This suggests that a maximal size and density of LDL were reached.



View larger version (22K):
[in this window]
[in a new window]
  		Figure 3. Proposed model of the combined effects of gender, IAF, and LIPC promoter genotype on HL activity. A, Elevated IAF and male gender are associated with higher HL activity. The magnitude of this association is dependent on the LIPC genotype. Higher HL activity promotes the conversion of HDL2 to HDL3 and the conversion of large, buoyant to small, dense LDL. In addition to the effect mediated by HL, IAF is associated with a residual increase in small, dense LDL. This pathway may be related to an increase in plasma TG, which stimulates CETP-mediated transfer of neutral lipids, leading to small, dense LDL. B, Gender, perhaps via estradiol, affects HL activity directly and indirectly via changes in IAF. Estradiol may also affect LDL size by the CETP-mediated effect of TG on LDL size.

 
A model (Fig. 3Go) that describes a possible relationship among central adiposity, gender, LIPC genotype, and HL is proposed with downstream effects on lipoproteins. HL increases with intraabdominal fat. The magnitude of this increase is affected by the LIPC genotype. Gender-related factors, presumably sex steroid hormones, act directly on HL activity, but also act indirectly via central adiposity. Higher HL activity increases the conversion of HDL2 to HDL3 (54) and the conversion of large, buoyant LDL to small, dense LDL (55). There is an additional influence of intraabdominal fat on LDL density beyond the effect of HL, perhaps by altering the synthesis of triglyceride-rich lipoproteins.

Sex steroid hormones were not measured in this cohort of men and premenopausal women. Estrogenic and androgenic steroids are produced by the ovary and testes (estradiol and testosterone), the adrenal gland (estrone and dehydroepiandrosterone), and peripheral adipose tissue conversion of androgens to estrogens (56). This complex list of sex steroids makes it difficult to know which hormones are most essential in regulating lipid metabolism. Postmenopausally, in some women HL activity is higher (24) and LDL particle size and buoyancy are lower than in premenopausal women (57). Some women also have increases in central adiposity across the menopause (58, 59). It is not known whether they are the same women who have elevated HL activity with menopause, but it is likely, because HL activity is positively associated with IAF (9).

Men had significantly higher body mass index and IAF than woman. At similar BMIs, the men had more than twice as much visceral fat as women, but had identical amounts of sc fat, and previous studies have shown that age-matched cohorts of men and women have significantly different BMI (50). After adjustment for IAF and genotype, the difference in BMI between men and women was erased. As has been shown previously (9, 18), HL activity is positively associated with IAF, but not BMI, in multiple regression analysis, and we have confirmed this finding.

In summary, gender differences in HL activity cannot be solely attributed to male/female differences in IAF. It appears that there is a residual effect of gender on HL activity that is not accounted for by IAF and may represent endogenous sex steroid hormones. Gender, visceral adiposity, and the HL gene promoter polymorphism appear to act independently to determine HL activity, and these factors account for 50% of the variance in HL activity. The influence of the HL gene promoter polymorphism on HL activity is similar in men and women, with the CC genotype having higher levels of HL activity independently of IAF.

Acknowledgments

We thank Alegria Aquino-Albers and Steve Hashimoto for their technical expertise, as well as Linda Floyd and Dr. Robert S. Schwartz for subject recruitment.

Footnotes

1 This work was supported by a grant from Bristol-Myers Squibb Co. Foundation; NIH Grants HL-30086, HL-64322, and NR-04141; the American Federation of Aging Research (to A.Z.); NIH Training Grant DK-07247 (to M.C.C.); and NIH Grant K23-RR-16067 (to M.C.C.). These studies were performed with the support of the University of Washington CNRU (DK-35816) and General Clinical Research Center (RR-37). Back

Received October 16, 2000.

Revised December 28, 2000.

Accepted March 2, 2001.

References

  1. Jansen H, van T-A, Hulsmann WC. 1980 On the metabolic function of heparin-releasable liver lipase. Biochem Biophys Res Commun. 92:53–59.[CrossRef][Medline]
  2. Jensen GL, Daggy B, Bensadoun A. 1982 Triacylglycerol lipase, monoacylglycerol lipase and phospholipase activities of highly purified rat hepatic lipase. Biochim BiophysActa.710:464–470.
  3. Kuusi T, Saarinen P, Nikkila EA.. 1980 Evidence for the role of hepatic endothelial lipase in the metabolism of plasma high density lipoprotein2 in man. Atherosclerosis. 36:589–593.[CrossRef][Medline]
  4. Zambon A, Austin MA, Brown BG, Hokanson JE, Brunzell JD. 1993 Effect of hepatic lipase on LDL in normal men and those with coronary artery disease. Arterioscler Thromb. 13:147–153.[Abstract/Free Full Text]
  5. Austin M, Breslow J, Hennekens C, Buring J, Willett W, Krauss R. 1988 Low-density lipoprotein subclass patterns and risk of myocardial infarction. JAMA. 260:1917–1921.[Abstract]
  6. Gordon DJ, Probstfield JL, Garrison RJ, et al. 1989 High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies. Circulation. 79:8–15.[Abstract/Free Full Text]
  7. Vega GL, Clark LT, Tang A, Marcovina S, Grundy SM, Cohen JC. 1998 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). J Lipid Res. 39:228–232.[Abstract/Free Full Text]
  8. Zambon A, Deeb SS, Hokanson JE, Brown BG, Brunzell JD. 1998 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. Arterioscler Thromb Vasc Biol. 18:1723–1729.[Abstract/Free Full Text]
  9. Despr’es JP, Ferland M, Moorjani S, et al. 1989 Role of hepatic-triglyceride lipase activity in the association between intra-abdominal fat and plasma HDL cholesterol in obese women. Arteriosclerosis.9:485–492.
  10. Huttunen JK, Ehnholm C, Kekki M, Nikkila EA. 1976 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. Clin Sci Mol Med. 50:249–260.[Medline]
  11. Krauss RM, Levy RI, Fredrickson DS. 1974 Selective measurement of two lipase activities in postheparin plasma from normal subjects and patients with hyperlipoproteinemia. J Clin Invest.54:1107–1124.
  12. Tikkanen MJ, Nikkila EA, Vartiainen E. 1978 Natural oestrogen as an effective treatment for type-II hyperlipoproteinaemia in postmenopausal women. Lancet. 2:490–491.[Medline]
  13. Ehnholm C, Huttunen JK, Kinnunen PJ, Miettinen TA, Nikkila EA. 1975 Effect of oxandrolone treatment on the activity of lipoprotein lipase, hepatic lipase and phospholipase A1 of human postheparin plasma. N Engl J Med. 292:1314–1317.[Abstract]
  14. Williams PT, Krauss RM. 1997 Associations of age: adiposity, menopause, and alcohol intake with low-density lipoprotein subclasses. Arterioscler Thromb Vasc Biol. 17:1082–1090.[Abstract/Free Full Text]
  15. Guerra R, Wang J, Grundy SM, Cohen JC. 1997 A hepatic lipase (LIPC) allele associated with high plasma concentrations of high density lipoprotein cholesterol. Proc Natl Acad Sci USA. 94:4532–4537.[Abstract/Free Full Text]
  16. Jansen H, Verhoeven AJ, Weeks L, et al. 1997 Common C-to-T substitution at position -480 of the hepatic lipase promoter associated with a lowered lipase activity in coronary artery disease patients. Arterioscler Thromb Vasc Biol. 17:2837–2842.[Abstract/Free Full Text]
  17. Peeples LH, Carpenter JW, Israel RG, Barakat HA. 1989 Alterations in low-density lipoproteins in subjects with abdominal adiposity. Metabolism. 38:1029–1036.[CrossRef][Medline]
  18. Carr MC, Hokanson JE, Deeb SS, Purnell JQ, Mitchell ES, Brunzell JD. 1999 A hepatic lipase gene promoter polymorphism attenuates the increase in hepatic lipase activity with increasing intra-abdominal fat in women. Arterioscler Thromb Vasc Biol. 19:2701–2707.[Abstract/Free Full Text]
  19. Williams PT, Krauss RM, Vranizan KM, Wood PD. 1990 Changes in lipoprotein subfractions during diet-induced and exercise-induced weight loss in moderately overweight men. Circulation. 81:1293–1304.[Abstract/Free Full Text]
  20. Purnell JQ, Kahn SE, Albers JJ, Nevin DN, Brunzell JD, Schwartz RS. 2000 Effect of weight loss with reduction of intra-abdominal fat on lipid metabolism in older men. J Clin Endocrinol Metab.85:977–982.
  21. Applebaum-Bowden D, Haffner SM, Wahl PW, et al. 1985 Postheparin plasma triglyceride lipases: relationships with very low density lipoprotein triglyceride and high density lipoprotein2 cholesterol. Arteriosclerosis. 5:273–282.[Abstract/Free Full Text]
  22. Tan CE, Foster L, Caslake MJ, et al. 1995 Relations between plasma lipids and postheparin plasma lipases and VLDL and LDL subfraction patterns in normolipemic men and women. Arterioscler Thromb Vasc Biol. 15:1839–1848.[Abstract/Free Full Text]
  23. Tikkanen MJ, Kuusi T, Nikkila EA, Stenman UH. 1986 Variation of postheparin plasma hepatic lipase by menstrual cycle. Metabolism. 35:99–104.[CrossRef][Medline]
  24. Ikenoue N, Wakatsuki A, Okatani Y. 1999 Small low-density lipoprotein particles in women with natural or surgically induced menopause. Obstet Gynecol. 93:566–570.[Abstract/Free Full Text]
  25. Applebaum DM, Goldberg AP, Pykalisto OJ, Brunzell JD, Hazzard WR. 1977 Effect of estrogen on post-heparin lipolytic activity. Selective decline in hepatic triglyceride lipase. J Clin Invest. 59:601–608.
  26. Taggart HM, Applebaum-Bowden D, Haffner S, et al. 1982 Reduction in high density lipoproteins by anabolic steroid (stanozolol) therapy for postmenopausal osteoporosis. Metabolism. 31:1147–1152.[CrossRef][Medline]
  27. Kannel WB, Hjortland MC, McNamara PM, Gordon T. 1976 Menopause and risk of cardiovascular disease: the Framingham study. Ann Intern Med. 85:447–452.
  28. Carlson LA, Ericsson M.. 1975 Quantitative and qualitative serum lipoprotein analysis. I. Studies in healthy men and women. Atherosclerosis. 21:417–433.[CrossRef][Medline]
  29. Heiss G, Tamir I, Davis CE, et al. 1980 Lipoprotein-cholesterol distributions in selected North American populations: the lipid research clinics program prevalence study. Circulation. 61:302–315.[Free Full Text]
  30. McNamara J, Campos H, Ordovas J, Peterson J, Wilson P, Schaefer E. 1987 Effect of gender, age, and lipid status on low density lipoprotein subfraction distribution. Results of the Framingham Offspring Study. Arteriosclerosis. 7:483–490.[Abstract/Free Full Text]
  31. Tikkanen MJ, Nikkila EA, Kuusi T, Sipinen SU. 1982 High density lipoprotein-2 and hepatic lipase: reciprocal changes produced by estrogen and norgestrel. J Clin Endocrinol Metab. 54:1113–1117.[Abstract]
  32. St-Amand J, Despres JP, Lemieux S, et al. 1995 Does lipoprotein or hepatic lipase activity explain the protective lipoprotein profile of premenopausal women? Metabolism. 44:491–498.[CrossRef][Medline]
  33. Lemieux S, Prud’homme D, Bouchard C, Tremblay A, Despr’es JP. 1993 Sex differences in the relation of visceral adipose tissue accumulation to total body fatness. Am J Clin Nutr. 58:463–467.[Abstract/Free Full Text]
  34. Mitchell ES, Woods NF. 1996 Symptom experiences of midlife women:observations from the Seattle Midlife Women’s Health Study. Maturitas. 25:1–10.[CrossRef][Medline]
  35. Rifkind BM, Segal P. 1983 Lipid Research Clinics Program reference values for hyperlipidemia and hypolipidemia. JAMA. 250:1869–1872.[Abstract]
  36. Warnick GR.. 1986 Enzymatic methods for quantification of lipoprotein lipids. Methods Enzymol. 129:101–123.[Medline]
  37. Iverius P, Brunzell J. 1985 Human adipose tissue lipoprotein lipase: changes with feeding in relation to postheparin plasma enzyme. Am J Physiol. 249:326–334.
  38. Hokanson JE. 2000 Measurement and clinical significance of low-density lipoprotein subclasses. In: Rifai N, Warnick G, Dominiczak M, eds. Handbook of lipoprotein testing. Washington DC: AACC Press; 329–344.
  39. Chung BH, Wilkinson T, Geer JC, Segrest JP. 1980 Preparative and quantitative isolation of plasma lipoproteins: rapid, single discontinuous density gradient ultracentrifugation in a vertical rotor. J Lipid Res. 21:284–291.[Abstract]
  40. Purnell JQ, Marcovina SM, Hokanson JE, et al. 1995 Levels of lipoprotein(a):apolipoprotein B, and lipoprotein cholesterol distribution in IDDM. Results from follow-up in the Diabetes Control and Complications Trial. Diabetes. 44:1218–1226.[Abstract]
  41. Miller SA, Dykes DD, Polesky HF. 1988 A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res.16:1215.
  42. Shuman WP, Morris LL, Leonetti DL, et al. 1986 Abnormal body fat distribution detected by computed tomography in diabetic men. Invest Radiol. 21:483–487.[Medline]
  43. Hokanson JE, Carr MC, Zambon A, Brunzell JD. 1998 Gender differences in hepatic lipase activity can be explained by differences in endogenous sex steroids [Abstract]. Circulation. 98(Supp 1):I-790.
  44. Sorva R, Kuusi T, Dunkel L, Taskinen MR. 1988 Effects of endogenous sex steroids on serum lipoproteins and postheparin plasma lipolytic enzymes. J Clin Endocrinol Metab. 66:408–413.[Abstract]
  45. Deeb SS, Peng R. 2000 The C-514T polymorphism in the human hepatic lipase gene promoter diminishes its activity. J Lipid Res. 41:155–158.[Abstract/Free Full Text]
  46. Terry RB, Stefanick ML, Haskell WL, Wood PD. 1991 Contributions of regional adipose tissue depots to plasma lipoprotein concentrations in overweight men and women: possible protective effects of thigh fat. Metabolism. 40:733–740.[CrossRef][Medline]
  47. Despres JP, Gagnon J, Bergeron J, et al. 1999 Plasma post-heparin lipase activities in the HERITAGE Family Study: the reproducibility, gender differences, and associations with lipoprotein levels. HEalth, RIsk factors, exercise Training and GEnetics. Clin Biochem. 32:157–165.[CrossRef][Medline]
  48. Schaefer EJ, Foster DM, Zech LA, Lindgren FT, Brewer Jr HB, Levy RI. 1983 The effects of estrogen administration on plasma lipoprotein metabolism in premenopausal females. J Clin Endocrinol Metab.57:262–267.
  49. Archer TK, Tam SP, Deeley RG. 1986 Kinetics of estrogen-dependent modulation of apolipoprotein A-I synthesis in human hepatoma cells. J Biol Chem. 261:5067–5074.[Abstract/Free Full Text]
  50. Freedman DS, Jacobsen SJ, Barboriak JJ, et al. 1990 Body fat distribution and male/female differences in lipids and lipoproteins. Circulation. 81:1498–1506.[Abstract/Free Full Text]
  51. Sattar N, Tan CE, Han TS, et al. 1998 Associations of indices of adiposity with atherogenic lipoprotein subfractions. Int J Obes Relat Metab Disord. 22:432–439.[CrossRef][Medline]
  52. Krauss RM, Lindgren FT, Ray RM. 1980 Interrelationships among subgroups of serum lipoproteins in normal human subjects. Clin Chim Acta.104:275–290.
  53. Zambon A, Hokanson JE, Brown BG, Brunzell JD. 1999 Evidence for a new pathophysiological mechanism for coronary artery disease regression: hepatic lipase-mediated changes in LDL density. Circulation. 99:1959–1964.[Abstract/Free Full Text]
  54. Deckelbaum RJ, Eisenberg S, Oschry Y, Granot E, Sharon I, Bengtsson-Olivecrona G. 1986 Conversion of human plasma high density lipoprotein-2 to high density lipoprotein-3. Roles of neutral lipid exchange and triglyceride lipases. J Biol Chem.261:5201–5208.
  55. Auwerx JH, Marzetta CA, Hokanson JE, Brunzell JD. 1989 Large buoyant LDL-like particles in hepatic lipase deficiency. Arteriosclerosis. 9:319–325.[Abstract/Free Full Text]
  56. O’Malley BW, Strott CA. 1999 Steroid hormones: metabolism and mechanism of action. In: Yen SSC, Jaffe RB, Barbieri RL, eds. Reproductive endocrinology, 4th Ed. Philadelphia: Saunders; 110–133.
  57. Campos H, McNamara JR, Wilson PW, Ordovas JM, Schaefer EJ. 1988 Differences in low density lipoprotein subfractions and apolipoproteins in premenopausal and postmenopausal women. J Clin Endocrinol Metab. 67:30–35.[Abstract]
  58. Ley CJ, Lees B, Stevenson JC. 1992 Sex- and menopause-associated changes in body-fat distribution. Am J Clin Nutr. 55:950–954.[Abstract/Free Full Text]
  59. Poehlman ET, Toth MJ, Gardner AW. 1995 Changes in energy balance and body composition at menopause: a controlled longitudinal study. Ann Intern Med. 123:673–675.[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 J. Clin. Endocrinol. Metab.Home page
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]

Home page
 J. Clin. Endocrinol. Metab.Home page
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]

Home page
 J. Nutr.Home page
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]

Home page
 JAMAHome page
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]

Home page
 J. Lipid Res.Home page
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]

Home page
 J. Lipid Res.Home page
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]

Home page
 Am. J. Clin. Nutr.Home page
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]

Home page
 J. Lipid Res.Home page
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]

Home page
 J. Clin. Endocrinol. Metab.Home page
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]

Home page
 Clin. Chem.Home page
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]

Home page
 J. Clin. Endocrinol. Metab.Home page
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]

Home page
 J. Clin. Endocrinol. Metab.Home page
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]

Home page
 J. Clin. Endocrinol. Metab.Home page
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]

Home page
 J. Am. Coll. Nutr.Home page
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]

Home page
 Hum Mol GenetHome page
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]

Home page
 J. Lipid Res.Home page
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]

Home page
 J. Lipid Res.Home page
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]

Home page
 J. Nutr.Home page
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]

Home page
 J. Clin. Endocrinol. Metab.Home page
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]

Home page
 J. Lipid Res.Home page
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]

Home page
 CirculationHome page
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]

Home page
 Am. J. Physiol. Endocrinol. Metab.Home page
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]

Home page
 Diabetes CareHome page
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]