Changes In Hepatic Lipase Activity Research Articles

The G-250A polymorphism in the hepatic lipase gene promoter is associated with changes in hepatic lipase activity and LDL cholesterol: The KANWU Study

Background and aims Hepatic lipase (HL) catalyzes the hydrolysis of triglycerides and phospholipids from lipoproteins, and promotes the hepatic uptake of lipoproteins. A common G-250A polymorphism in the promoter of the hepatic lipase gene (LIPC) has been described. The aim was to study the effects of the G-250A polymorphism on HL activity, serum lipid profile and insulin sensitivity. Methods and results Altogether 151 healthy subjects (age 49 ± 8 years, BMI 26.5 ± 3.0 kg/m 2) were randomly assigned for 3 months to an isoenergetic diet containing either a high proportion of saturated fatty acids (SFA diet) or monounsaturated fatty acids (MUFA diet). Within groups there was a second random assignment to supplements with fish oil (3.6 g n-3 FA/day) or placebo. At baseline, the A-250A genotype was associated with high serum LDL cholesterol concentration ( P = 0.030 among three genotypes). On the MUFA diet carriers of the A-250A genotype presented a greater decrease in LDL cholesterol concentration than subjects with other genotypes ( P = 0.007 among three genotypes). The rare -250A allele was related to low HL activity ( P < 0.001 among three genotypes). The diet did not affect the levels of HL activity among the genotypes. Conclusion The A-250A genotype of the LIPC gene was associated with high LDL cholesterol concentration, but the MUFA-enriched diet reduced serum LDL cholesterol concentration especially in subjects with the A-250A genotype.

Hepatic Lipase as a Focal Point for the Development and Treatment of Coronary Artery Disease

Recent epidemiological evidence suggests that although lowering low-density lipoprotein (LDL) cholesterol is important in decreasing cardiovascular disease morbidity and mortality, it accounts only for part of the coronary artery disease...

Alterations in hepatic lipase and lipoprotein subfractions with transdermal testosterone replacement therapy.

The effect of sex hormone replacement therapy on lipoprotein metabolism is thought to be less marked with the transdermal route because of the lack of hepatic first-pass effect. The aim of this study was to evaluate the effects of testosterone replacement therapy given transdermally via a permeation-enhanced system on plasma lipolytic enzymes (hepatic and lipoprotein lipase), LDL and HDL subfraction concentrations. Ten patients with primary testicular failure were started on transdermal testosterone (Testoderm(R)). Plasma lipids, lipoproteins and post-heparin plasma lipolytic enzymes were evaluated before and after 3 months of treatment. LDL and HDL subfractions were measured by density gradient ultracentrifugation and hepatic and lipoprotein lipase activities by radio-enzymatic method. Serum testosterone level increased to within the normal range in all subjects whereas serum dihydrotestosterone (DHT) increased to supra-normal values. Plasma hepatic lipase (HL) activity increased after testosterone replacement (24.7 +/- 7.5 vs. 29.2 +/- 8.3 micromol free fatty acid released per hour, P < 0.05) and the increase in HL correlated with the increase in DHT (r = 0.64, P < 0. 05). Small changes were observed in LDL subfraction pattern with an increase in the concentration of small dense LDL-III (80.1 +/- 30.3 vs. 93.0 +/- 27.8 mg/l, P < 0.05). No significant change was seen in the HDL2 subfraction but HDL3 decreased after treatment (0.93 +/- 0. 17 vs. 0.79 +/- 0.14 mmol/l, P < 0.01). Testosterone replacement, given via a permeation-enhanced transdermal system, is associated with changes in hepatic lipase activity and in LDL and HDL subfractions. Whether these changes adversely influence the cardiovascular risk in the longterm remains to be determined.

Induction of Adrenal Scavenger Receptor BI and Increased High Density Lipoprotein-Cholesteryl Ether Uptake by in Vivo Inhibition of Hepatic Lipase

Hepatic lipase (HL) and scavenger receptor type B class I (SR-BI) have both been implicated in high density lipoprotein (HDL)-cholesteryl ester uptake in cholesterol-utilizing tissues. Inactivation of HL by gene-directed targeting in mice results in up-regulation of SR-BI expression in adrenal gland (Wang, N., Weng, W., Breslow, J. L., and Tall, A. R. (1996) J. Biol. Chem. 271, 21001-21004). The net effect on HDL-cholesteryl ester uptake is not known. We determined the impact of acute in vivo inhibition of rat adrenal HL activity by antibodies on SR-BI expression and on human and rat HDL-[3H]cholesteryl ether (CEth) uptake in the adrenal gland. Rat HDL was isolated from rats in which HL activity had been inhibited for 1 h. The rats were studied under basal conditions (not ACTH-treated) and after previous treatment with ACTH for 6 days (ACTH-treated). Intravenous injection of anti-HL resulted in 70% lowering of adrenal HL activity in both conditions which were maintained for at least 8 h. In not ACTH-treated rats, inhibition of adrenal HL increased adrenal SR-BI mRNA (5.2-fold) and mass (1. 6-fold) within 4 h. HL inhibition resulted in 41% and 14% more adrenal accumulation of human HDL-[3H]CEth during 4 and 24 h, respectively. The adrenal uptake of rat HDL-[3H]CEth increased by 68%, 4 h after the antibody injection. ACTH treatment increased total adrenal HL activity from 3.7 +/- 0.5 milliunits to 34.0 +/- 17. 2 milliunits, as well as adrenal SR-BI mRNA from 2.9 +/- 0.7 arbitrary units (A.U.) to 86.8 +/- 41.1 A.U. and SR-BI mass from 7.7 +/- 1.8 A.U. to 63.16 +/- 46.7 A.U. The human HDL-[3H]CEth uptake by adrenals was also significantly increased from 0.58 +/- 0.11% of injected dose to 7.24 +/- 1.58% of injected dose. Inhibition of adrenal HL activity did not result in further induction of SR-BI expression and did not affect human HDL-[3H]CEth uptake. These findings indicate that SR-BI expression may be influenced by changes in HL activity. HL activity is not needed for the SR-BI-mediated HDL-cholesteryl ester uptake by rat adrenal glands.

Change in dietary saturated fat intake is correlated with change in mass of large low-density-lipoprotein particles in men

We tested whether nutrient intakes estimated from 4-d diet records were associated with plasma lipoprotein subclasses in 103 men who were randomly assigned to a low-fat (24% fat) and a high-fat (46% fat) diet for 6 wk each in a crossover design. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activities were also determined in a subset of 43 men. Changes in intake (ie, high fat minus low fat) of total saturated fatty acids, as well as myristic (14:0) and palmitic (16:0) acids, were positively correlated (P < 0.01) with increases in mass of large LDL particles [measured by analytic ultra-centrifugation as mass of lipoproteins of flotation rate (Sf) 7-12] and with LDL peak particle diameter and flotation rate, but not with changes in LDL-cholesterol concentration. Changes in total saturated fatty acids as well as myristic and palmitic acids were also inversely associated with changes in HL activity (P < 0.05). With the high-fat diet only, variation in dietary total saturated fatty acid intake was inversely correlated (P < 0.01) with concentrations of small, dense LDL of Sf 0-5. This correlation was significant specifically for myristic acid (P < 0.001). Stearic acid (18:0), monounsaturates, and polyunsaturates showed no significant associations with lipoprotein concentrations. These data indicate that a high saturated fat intake (especially 14:0 and 16:0) is associated with increased concentrations of larger, cholesterol-enriched LDL and this occurs in association with decreased HL activity.

Relations between thyroid function, hepatic and lipoprotein lipase activities, and plasma lipoprotein concentrations.

Lipoprotein concentrations and activities of lipoprotein lipase (LPL) and hepatic lipase (HL) were measured in 70 subjects with thyroid function ranging from overt hypothyroidism over subclinical hypothyroidism and euthyroidism to hyperthyroidism. In parallel with serum T3 (S-T3) concentrations increasing from low in hypothyroidism to high in hyperthyroidism there were gradually higher HL activities over the full spectrum of thyroid function, accompanied by decreasing levels of total and low density lipoprotein (LDL) cholesterol. High density lipoprotein (HDL) cholesterol was lower (P less than 0.05) in hyperthyroidism than in euthyroidism but not significantly changed in the hypothyroid groups. HL was correlated to S-T3 (r = 0.77, P less than 0.001), LDL cholesterol to log S-T3 (r = -0.76, P less than 0.001), and LDL cholesterol to log HL (r = -0.55, P less than 0.001). The activity of LPL was decreased (P less than 0.001) in overt hypothyroidism compared to euthyroidism but, in contrast to HL, the activity of LPL was not increased in hyperthyroidism. The plasma triglyceride (P-TG) concentration was elevated (P less than 0.01) in overt hypothyroidism but not significantly changed in subclinical hypothyroidism or in hyperthyroidism. The LPL activity was correlated to log S-T3 (r = 0.45, P less than 0.001), P-TG to log S-T3 (r = -0.37, P less than 0.01) and P-TG to log LPL activity (r = -0.71, P less than 0.001). Our results demonstrate that thyroid hormones influence HL and LPL activities in different ways, suggesting different mechanisms of action. Changes in HL activity seem to be an important mechanism for the disturbance of cholesterol metabolism in thyroid dysfunction while the thyroid hormone influence on LPL seems to be of importance mainly for the disturbance in triglyceride metabolism.

High density lipoprotein-2 and hepatic lipase: reciprocal changes produced by estrogen and norgestrel.

The concentrations of plasma high density lipoprotein (HDL) and its subfraction HDL2 are influenced by endogenous and exogenous sex hormones. The catabolism of HDL2 is mediated by a lipolytic enzyme, hepatic lipase, which is present in endothelial cells covering the liver sinusoids. Since the activity of this enzyme is also regulated by gonadal and anabolic steroids, we examined whether the effect of sex steroids on plasma HDL is related to changes in hepatic lipase. In postmenopausal women, estradiol valerate (2 mg/day, orally) increased the HDL2 cholesterol and phospholipid concentrations by 20% (P less than 0.05). Simultaneously, the hepatic lipase activity of postheparin plasma decreased by 25% (P less than 0.05). The addition of levonorgestrel (250 micrograms/day, orally) to the treatment reversed both effects of estrogen, so that HDL2 cholesterol and phospholipid levels fell below and hepatic lipase activity rose above the respective pretreatment values. The hormones did not influence the HDL3 lipid concentrations or the lipoprotein lipase and lecithin:cholesterol acyltransferase activities. The results are compatible with the hypothesis that the effects of sex steroids on plasma HDL (HDL2) are mediated by changes in hepatic lipase activity.

Activities of post-heparin plasma lipoprotein lipase and hepatic lipase during pregnancy and lactation.

Abstract. The marked increase in serum triglyceride (TG) in women during pregnancy and lactation was studied. Hormone concentrations, changes in activities of post‐heparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) were correlated with plasma lipoprotein concentrations. The plasma concentrations of free oestriol, oestradiol and prolactin were estimated, and analyses of very low density lipoprotein triacylgly‐cerol (VLDL‐TG), and low density (LDL‐Chol) and high density lipoprotein cholesterol (HDL‐Chol) were performed. Post‐heparin plasma LPL and H L activities were selectively measured by an immunochemical method. LPL activity was unaltered during pregnancy and immediately after parturition, values ranging from ll.5 ± l.9 to 12.9 ± l.2 µimol free fatty acid (FFA)/ml/h. Eight weeks after parturition LPL activity was increased to 22.1 ± 5.5 µmiol FFA/ml/h. There was a significant negative correlation between LPL activity and VLDL‐TG concentration in plasma (r= ‐0.58; P &lt; 0.01). The mean HL activity was 7.8 ± 1.9 and 6.4 ± 1.5 µxmol FFA/ml/h during mid‐and late pregnancy, respectively, and after parturition the activity increased from 13.5 ± 30 to 32.4 ± 7.5 µol FFA/ml/h in samples taken 3 days and 8 weeks after parturition. In spite of the changes in HL activity no correlation was found between HL activity and the concentrations of plasma lipoprotein lipids. HL activity bore a significant negative correlation with plasma free oestriol (r= ‐0.46; P &lt; 005), oestradiol (r= ‐0.57; P &lt; 001) and prolactin (r= ‐0.76; P &lt; 0001) levels. Since oestrogens are known to reduce HL activity, the increase in plasma HL activity during the postpartum period may be caused by the concomitant fall of plasma oestrogen levels. Plasma HDL‐Chol and LDL‐Chol did not vary despite the considerable changes in oestrogen, prolactin and VLDL‐TG levels and HL activity. The increase in plasma VLDL‐TG concentration during pregnancy occurred concomitantly with the increase in unconjugated plasma oestriol, oestradiol and prolactin levels, but it was not associated with any changes in LPL activity. In the second trimester, LPL activity was 12.9 ± 116 (mean ± SEM) µmol FFA/ml/h, which is about 50% of the activity reported for the corresponding age group of nonpregnant women. Thus, lowered removal capacity by extrahepatic tissues is likely to cause the moderate rise in the VLDL‐TG (0.84 ± 0–17 mmol l‐1, mean ± SEM) in the second trimester. At the 38th week of gestation LPL activity was similar to the level seen in midpregnancy, but still the VLDL‐TG was greatly increased (2.85 ± 0.66 mmol l‐1, mean ± SEM). Both oestradiol and prolactin bore a significant positive correlation with the levels of plasma VLDL‐TG (r= 0.52; P &lt; 001 and r= 0.42; P &lt; 0.05, respectively). The present data suggests that the massive pregnancy associated hypertriglyceridaemia is not caused solely by impaired removal of VLDL‐TG by extrahepatic LPL, but is mainly due to the increased synthesis of VLDL‐TG caused by the increased levels of plasma oestrogens.