Effect of gemfibrozil on the regulation of HDL subfractions in hypertriglyceridaemic patients

Abstract. Objectives . To study changes of HDL subfractions and their regulation during gemfibrozil treatment in hypertriglyceridaemia. Design . Twenty patients with hypertriglyceridaemia were randomized to receive either 1200 mg day^-1gemfibrozil or placebo for 3 months. After a 6-week, single-blind placebo period, the patients were randomized to receive either gemfibrozil or placebo for 3 months in a double-blind study. Setting . The patients were studied as outpatients in the Third Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland. Main outcome measures . Ultracentrifugally isolated HDL subclasses; concentrations of apoA-I, apoA-II, LpA-I and LpA-I: A-II particles; post-heparin plasma lipoprotein lipase (LPL), hepatic lipase (HL) and plasma cholesteryl ester transfer protein (CETP) activities; phospholipid transfer protein (PLTP) and lecithine cholesteryl acyltransferase (LCAT) activities were measured in plasma from six patients from both groups. Results . Gemfibrozil increased the concentration of HDL cholesterol (+ 11.1%) because of the rise of HDL₃ cholesterol (34.5%, P < 0.01). The concentration of LpA-I particles was reduced during gemfibrozil treatment (–12.4%, P < 0.05), while that of apoA-II increased (+ 12.3%, P < 0.01). The LpA-I to LpA-I:A-II ratio decreased significantly in the gemfibrozil group (–18.9%, P < 0.01). Gemfibrozil increased LPL and HL activities by 18.2% (P < 0.05) and by 19.6%, respectively. Plasma CETP activity was also increased during gemfibrozil treatment (+15.8%, P < 0.05). Conclusion . The gemfibrozil-induced elevation of HDL₃ and apoA-II may reflect the combined action of LPL, HL and CETP on plasma HDL metabolism.     

High density lipoprotein, apoproteins A-I and A-II and postheparin plasma lipolytic enzymes after ileal bypass

Apoproteins A-I and A-II, and the activities of lipoprotein lipase (LPL) and hepatic lipase (HL), were studied in 16 patients 3-12 years after ileal bypass operation and in 13 controls, all heterozygous for familial hypercholesterolemia, to investigate why the operated subjects had a higher HDL cholesterol level than the unoperated controls. HDL- and HDL2-cholesterol and apoprotein A-I were higher, HDL3-cholesterol was similar and apoprotein A-II tended to be lower in the operated than the control subjects. The activities of LPL and HL were similar in the 2 groups. HL was negatively correlated with HDL2-cholesterol, whereas LPL was not associated with any of the HDL components. The controls had gained in weight during the follow-up, but the HDL components were not correlated with relative body weight. It is concluded that in familial hypercholesterolemia ileal bypass results in higher HDL- and HDL2-cholesterol and apoprotein A-I level than conservative treatment and that postheparin plasma lipolytic enzymes do not explain the higher level of these HDL components in the operated subjects.     

脑梗死患者血浆HDL亚类组成及含量研究

目的:分析脑梗死患者血浆高密度脂蛋白(HDL)亚类组成及含量。方法:采用双向电泳-免疫印迹检测法分析50例脑梗死患者和50例正常者HDL亚类的组成及含量。结果:与对照组比较,脑梗死患者血浆中preβ2-HDL和HDL2b含量显著降低(均P<0.01),小颗粒preβ1-HDL含量显著增加(P<0.01);患者血浆三酰甘油(TG)水平与preβ1-HDL、HDL3b、HDL2a和HDL2b含量呈显著负相关(均P<0.05),HDL-C、载脂蛋白AⅠ含量与preβ1-HDL、preβ2-HDL、HDL3c、HDL3b、HDL3a、HDL2a和HDL2b含量呈显著正相关(均P<0.05)。结论:脑梗死患者血浆大颗粒HDL含量明显降低,小颗粒HDL含量明显增加,提示脑梗死患者HDL代谢过程异常。     

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

Abdominal obesity is associated with numerous metabolic alterations, such as hypertriglyceridemia and low levels of high density lipoprotein (HDL) cholesterol. However, compared with abdominally obese white individuals, abdominally obese black individuals have been characterized by higher plasma HDL cholesterol levels, suggesting that the impact of abdominal fat accumulation on the lipoprotein-lipid profile may differ among ethnic groups. Therefore, we have compared the associations between body fatness, visceral adipose tissue (AT) accumulation, and metabolic risk variables in a sample of 247 white men and 240 white women versus a sample of 93 black men and 143 black women. Although no difference in mean total body fatness was found between the 2 race groups, white men had higher levels of visceral AT than did black men (P<0.001). Despite the fact that black women had a greater body fat content than did white women, black women had levels of visceral AT that were similar to those of white women, suggesting a lower susceptibility to visceral obesity in black women. This lower accumulation of visceral AT in blacks was accompanied by significantly reduced apolipoprotein B concentrations and ratios of total cholesterol to HDL cholesterol as well as higher plasma HDL cholesterol levels (P<0.05) compared with those values in whites. Irrespective of sex, higher postheparin plasma hepatic lipase (HL) and lower lipoprotein lipase (LPL) activities were found in whites, resulting in an HL/LPL ratio that was twice as high in whites as in blacks (P<0.005). Although differences in lipoprotein-lipid levels were noted between whites and blacks, results from multiple regression analyses revealed that after control for morphometric and metabolic variables of the study (body fat mass, visceral AT, LPL, HL, and age), ethnicity had, per se, only a minor contribution to the variance in plasma lipoprotein levels. Thus, our results suggest that the higher plasma HDL cholesterol levels and the generally more cardioprotective plasma lipoprotein profile found in abdominally obese black versus white individuals are explained, at least to a certain extent, by a lower visceral AT deposition and a higher plasma LPL activity in black individuals.     

Lipoprotein lipase prevents the hepatic lipase-induced reduction in particle size of high density lipoproteins during incubation of human plasma

Human plasma lipoproteins or human whole plasma have been incubated in vitro with canine hepatic lipase (HL) and bovine milk lipoprotein lipase (LPL) to determine the effects of lipases on the particle size distribution of HDL. Confirming previous reports, HL preferentially hydrolysed high density lipoprotein (HDL) triacylglycerol while LPL hydrolysed predominantly very low density lipoprotein (VLDL) triacylglycerol; however, neither lipase altered HDL particle size unless both VLDL and cholesteryl ester transfer protein (CETP) were present. Under these conditions HL promoted marked reduction in HDL particle size in a process dependent on the concentration of VLDL triacylglycerol while LPL was virtually without effect. When both LPL and HL were included in the same incubation, however, LPL prevented the effects of HL. These results are consistent with a proposition that HL has a direct effect on HDL particle size in a process which is dependent on concurrent lipid transfers between HDL and VLDL and that LPL reduces the effect of HL by reducing the concentration of VLDL triacylglycerol.     

Correlation between the activities of lipoprotein lipase and paraoxonase in type 2 diabetes mellitus

In type 2 diabetes mellitus the decreased catabolism of triglyceride-rich lipoproteins as a consequence of mainly the decreased lipoprotein lipase activity results in hypertriglyceridaemia and other lipoprotein alterations promoting atherosclerosis. The high-density lipoprotein-associated enzyme, paraoxonase, prevents the oxidation of low-density lipoprotein, which is an antiatherogenic effect.

Aim

to examine the relation between the activities of enzymes influencing HDL remodelling- LPL and PON- in type 2 diabetes mellitus.

Methods

56 newly diagnosed type 2 diabetic patients and 39 healthy controls were involved in the study. The serum PON activity was measured spectrophotometrically using paraoxone as substrate. PON phenotype was determined by the dual substrate method, PON mass was measured by ELISA. The determination of lipoprotein lipase activity was performed using ³H-triolein.

Results

We noticed smaller PON activity decrease in our newly diagnosed diabetic subjects compared to the previous studies which investigated the alteration of enzyme activity after a longer duration of diabetes mellitus. The lipoprotein lipase activity showed a positive correlation with PON activity (r = 0.43; P < 0.02). Interestingly, the PON activity of the homozygous-low activity group did not correlate with the LPL activity, while in the heterozygous and homozygous-high activity groups there was a significantly positive correlation (r = 0.51; P < 0.05) between PON and LPL activity.

Conclusion

Besides lipid alterations, the metabolic changes of type 2 diabetes mellitus influence the reduction of the antioxidant capacity of HDL by remodelling HDL and decreasing PON activity via modification of lipoprotein lipase activity, which might contribute to accelerated atherosclerosis.     

Catabolic defect of triglyceride is associated with abnormal very-low-density lipoprotein in experimental nephrosis

Very-low-density lipoprotein (VLDL)-triglyceride (TG) kinetics were examined in puromycin aminonucleoside-induced nephrotic rats in order to establish the nature of the hypertriglyceridemia associated with this condition. Nephrotic rats had a plasma TG concentration 10-fold higher than the controls. In nephrotic rats TG secretion rate was elevated only 1.2-fold above the controls, suggesting that the catabolism of TG was also impaired. Lipolytic activities were determined in postheparin plasma (PHP) of the control and the nephrotic rats. There were no significant differences in either the activity of lipoprotein lipase (LPL) or hepatic lipase (HL). VLDL-TG was endogenously radiolabeled in donor rats with [2-3H]-glycerol. The half life (T1/2) was then determined by monitoring the clearance of plasma [3H]-VLDL-TG in normal recipient animals. The T1/2 of VLDL-TG from nephrotic rats was twice that of normal rats. The defect in VLDL-TG clearance could be partially rectified by preincubation with high-density lipoprotein (HDL) from normal rats, but not with HDL from nephrotic rats. VLDL from either nephrotic or normal rats were incubated with PHP of normal rats to assess the effectiveness of VLDL-TG as a substrate for PHP. The lipolytic rate for nephrotic VLDL was significantly lower than that for normal VLDL, suggesting that VLDL from nephrotic rats was somewhat resistant to the action of LPL and HL. When VLDL from nephrotic rats was preincubated with HDL from normal rats, the low lipolytic rate of VLDL-TG improved significantly. This was not observed when HDL from nephrotic rats was used for the preincubation. The results suggested that physical and/or chemical change of VLDL particles due to nephrosis results in a catabolic defect of VLDL-TG.     

Testosterone substitution increases the activity of lipoprotein lipase and hepatic lipase in hypogonadal males

We studied the effects of testosterone substitution on serum concentrations of lipids, lipoproteins, apoproteins and on the activity of hepatic lipase (HL) and lipoprotein lipase (LPL) in postheparin plasma and on the activity of LPL in adipose tissue (AT-LPL) in 13 male hypopituitary patients. The activities of LPL and HL in postheparin plasma were markedly increased by 1 week after a testosterone enanthate injection (P less than 0.001). The HL activity remained elevated (P less than 0.05) after 1 month's treatment, but the LPL activity declined to presubstitution levels. The prolonged substitution decreased serum apoproteins A-I and A-II (P less than 0.05). The changes of apo A-I and A-II correlated inversely with those of the free testosterone index (FTI) (r = -0.74, r = -0.67, P less than 0.05). Serum HDL-cholesterol level decreased slightly by 1 week and it correlated inversely with the increase in testosterone and the FTI (r = -0.67, r = -0.85, P less than 0.05). The results suggest that testosterone increases the activity of both lipolytic enzymes in postheparin plasma. The effect on HL appears to be more persistent than that on LPL. The data support a role for androgens in the regulation of serum lipoprotein and HDL-cholesterol levels.     

Changes in serum lipoprotein pattern induced by acute infections

To study the effects of acute infections on serum lipids and lipoproteins we measured the concentration and composition of different lipoproteins, apoproteins A-I, A-II, and B, and the activities of plasma postheparin lipolytic enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL) during acute and convalescence phase and after complete recovery in 72 infectious patients (33 with viral infection and 39 with bacterial infection). The mass concentrations of both low density lipoprotein (LDL) (P less than .001) and high density lipoprotein (HDL)2 (P less than .002) were reduced during acute infections due to the lowering of their cholesterol, phospholipid, and protein contents. The reduction of LDL cholesterol was maximal at the acute stage of infection (change -15%, P less than .001) while the reduction of HDL2 cholesterol was maximal during the convalescence (change -35%, P less than .001). During acute infections LDL became triglyceride-enriched (11.8 v 8.6%, P less than .0001) but cholesterol-poor (36.6 v 39.3%, P less than .0001). The ratio of HDL cholesterol/LDL cholesterol was significantly reduced during the convalescence (0.42 +/- 0.15 v 0.53 +/- 0.19, P less than .0001). The concentrations of apo A-I and apo A-II were decreased during acute infections (changes -22%, P less than .001, and -16%, P less than .001, respectively). The very low density lipoprotein (VLDL) was 18% higher during the convalescence period than after the recovery due to the elevations of VLDL triglycerides, cholesterol, and phospholipids. The activity of LPL was reduced both in the acute and convalescence phase, whereas that of HL was reduced only in the acute phase of infections.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Long-term Therapy with Labetalol on Lipoprotein Metabolism in Patients with Mild Hypertension

ABSTRACT. The effects of labetalol on serum lipoproteins, the intravenous fat tolerance test (IVFTT) and lipoprotein lipase (LPL) and hepatic lipase (HL) activities were studied in 16 patients with mild hypertension before and after 6 months of therapy. Most patients were found to be normotensive on 200 mg labetalol/day. Before therapy the mean concentration of serum TG was 0.75 ± 0.21 (SD) mmol/1, of total cholesterol 5.41 ± 1.25 mmol/1 and of HDL cholesterol 1.67 ± 0.61 mmol/1. After labetalol no significant changes were found in the concentrations of TG and cholesterol in the VLDL, LDL and HDL fractions. The mean values for the IVFTT and for LPL and HL activities were in the normal range and remained unchanged during therapy.     

Lipoprotein and hepatic lipase activity and high-density lipoprotein subclasses after cardiac transplantation

Atherosclerosis is the leading obstacle to long-term survival in cardiac transplant patients. Increases in plasma triglycerides and lipoprotein cholesterol levels occur after transplantation that may contribute to transplant atherosclerosis. The etiology of this increase is unclear. We investigated the interaction of immunosuppressive medications with plasma triglycerides, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, the HDL subclasses HDL2 and HDL3 cholesterol, and hepatic and lipoprotein lipase activity in 72 consecutive cardiac transplant patients compared to 51 healthy control subjects. In the transplantation group, greater concentrations of plasma triglyceride (80%, p less than 0.001), LDL cholesterol (16%, p less than 0.005) and hepatic lipase activity (100%, p less than 0.001) were noted, whereas lipoprotein lipase activity was noted to be significantly lower (124%, p less than 0.001). No difference was detected in HDL, HDL2, or HDL3 cholesterol. Cyclosporine dose was significantly associated with hepatic lipase activity (r = 0.33, p less than 0.02) and inversely associated with lipoprotein lipase activity (r = -0.28, p less than 0.05). Lipoprotein lipase activity after transplantation correlated inversely with triglycerides (r = -0.36, p less than 0.002) and positively with HDL cholesterol (r = 0.23, p less than 0.05) and HDL2 cholesterol (r = 0.29, p less than 0.05). Hepatic lipase activity correlated inversely with LDL cholesterol (r = -0.21, p less than 0.08). In multiple regression analysis, cyclosporine dose was the major source of variation in hepatic lipase activity.     

Overexpression of human hepatic lipase and ApoE in transgenic rabbits attenuates response to dietary cholesterol and alters lipoprotein subclass distributions

The effect of the expression of human hepatic lipase (HL) or human apoE on plasma lipoproteins in transgenic rabbits in response to dietary cholesterol was compared with the response of nontransgenic control rabbits. Supplementation of a chow diet with 0.3% cholesterol and 3.0% soybean oil for 10 weeks resulted in markedly increased levels of plasma cholesterol and VLDL and IDL in control rabbits as expected. Expression of either HL or apoE reduced plasma cholesterol response by 75% and 60%, respectively. The HL transgenic rabbits had substantial reductions in medium and small VLDL and IDL fractions but not in larger VLDL. LDL levels were also reduced, with a shift from larger, more buoyant to smaller, denser particles. In contrast, apoE transgenic rabbits had a marked reduction in the levels of large VLDLs, with a selective accumulation of IDLs and large buoyant LDLs. Combined expression of apoE and HL led to dramatic reductions of total cholesterol (85% versus controls) and of total VLDL+IDL+LDL (87% versus controls). HDL subclasses were remodeled by the expression of either transgene and accompanied by a decrease in HDL cholesterol compared with controls. HL expression reduced all subclasses except for HDL2b and HDL2a, and expression of apoE reduced large HDL1 and HDL2b. Extreme HDL reductions (92% versus controls) were observed in the combined HL+apoE transgenic rabbits. These results demonstrate that human HL and apoE have complementary and synergistic functions in plasma cholesterol and lipoprotein metabolism.     

高脂血症性急性胰腺炎脂蛋白脂酶基因多态性研究

目的 探讨三酰甘油分解代谢酶脂蛋白脂酶(LPL)的表达和基因多态性与高脂血症性急性胰腺炎(HLP)的相关性.方法 2005年5月至2006年12月HLP住院患者20例,急性胰腺炎患者50例,另选取血脂正常患其他疾病者50例为对照.测定血清三酰甘油(TG)、胆固醇(Ch)、游离脂肪酸(FFA)、脂蛋白数值、血清LPL/肝脂酶(HL)活性;RT-PCR检测LPL mRNA表达;聚合酶链-限制性酶切片段多态性分析(PCR-RFLP)法分析LPL基因内含子8 Hind Ⅲ基因多态性变化.结果 HLP组血清TG、胆固醇(Ch)和FFA测定值均显著高于AP组和对照组,差异均有统计学意义(P值均<0.05);HLP组ApoE值显著高于AP组和对照组(P<0.05);HLP组高密度脂蛋白(HDL)显著低于对照组(P<0.05).HLP组LPL值为(5.98±2.28)U/L,均显著高于AP组和对照组[(1.97±0.76)U/L和(1.04±0.53)U/L,P值分别=0.046和0.031];HLP组HL值为(8.15±2.86)U/L,均显著高于AP组和对照组(1.64±0.59)U/L和(0.86±0.39)U/L,P值分别=0.002和0.001].HLP组LPL mRNA表达高于AP组,差异有统计学意义(P=0.0325).LPL基因内含子8 Hind Ⅲ分析,H2等位基因频率HLP组显著高于对照组(0.90比0.72,P<0.05);H1等位基因频率在HLP和AP组均显著低于对照组(0.10比0.28和0.14比0.28,P<0.05).HLP组H2H2基因型患者TG和Apo E值均显著高于H2H1/H1H1基因型(P值分别=0.043和0.046);AP组H2H2基因型患者TG值显著高于H2H1/H1H1基因型(P=0.032).结论 HLP患者LPL Hind Ⅲ H2等位基因频率显著高于正常人群,主要与高三酰甘油血症(HTG)相关,而与胰腺炎无关;且H2H2基因型的HLP患者血清TG、ApoE值高于其他基因型者.HTG可引起LPL基因和蛋白表达活性增高,加速TG大量分解代谢和FFA等分解产物蓄积,是诱发和加重HLP的中心环节和重要病理生理机制.     

Tibolone lowers high density lipoprotein cholesterol by increasing hepatic lipase activity but does not impair cholesterol efflux

OBJECTIVE: Androgens and other drugs that reduce plasma concentrations of high density lipoprotein (HDL) cholesterol are often considered to be pro-atherogenic. Tibolone lowers HDL-cholesterol by 20% but the clinical significance of this effect is unknown. METHODS: In a randomized, double-blind study, 34 women received 2.5 mg tibolone daily and 34 women received placebo. Serum concentrations of lipids, lipoprotein subclasses and apolipoproteins, together with plasma activities of lipid transfer proteins and lipolytic enzymes and the capacity of plasma to induce cholesterol efflux from cultured cells, were measured. RESULTS: Compared to placebo, tibolone reduced serum concentrations of HDL-cholesterol (-14%), HDL phosphatidylcholine (-14%), apolipoprotein (apo)A-I (-12%), HDL subclasses lipoprotein (Lp)A-I (-20%), HDL-apoE (-16%), pre beta-LpA-I (-10%) and alpha-LpA-I (-12%) and increased hepatic lipase activity (+25%) and HDL sphingomyelin : phosphatidylcholine ratio (10.5%), but did not alter serum concentrations of HDL sphingomyelin, apoA-IV and LpA-I/A-II, lipoprotein lipase, the plasma activities of lecithin : cholesterol acyl transferase, cholesteryl ester transfer protein, phospholipid transfer protein or the plasma capacity to release cholesterol from cultured fibroblasts or Fu5AH hepatocytes. CONCLUSIONS: Tibolone lowers HDL-cholesterol in part by increasing hepatic lipase activity. Conservation of sphingomyelin and apoA-II in HDL, as well as cholesteryl ester transfer protein activity, preserves the capacity of plasma to release cholesterol, despite the lower concentrations of HDL-cholesterol. This may have important implications for the use of steroid effects on HDL concentrations as surrogates for atherosclerosis.     

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

OBJECTIVES: 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. MEASUREMENTS: 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. RESULTS: 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). CONCLUSIONS: 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.     

Cardiovascular fitness, body composition, and lipoprotein lipid metabolism in older men

BACKGROUND: Lipoprotein lipids in older individuals are affected by family history of coronary artery disease (CAD), obesity, diet, and physical activity habits. METHODS: The relationship of obesity and physical fitness (VO2max) to lipoprotein lipids and postheparin lipases was examined in a cross-sectional study of 12 lean (LS) and 26 obese (OS) sedentary men and 18 master athletes (MAs) aged 65+/-1 years (mean +/- SE). The men were healthy, had no family history of CAD, and were weight stable on AHA diets at the time of study. RESULTS: VO2max was similar in LS and OS men but higher in the MAs. The OS men had a higher percentage of body fat (%BF), waist circumference, and waist:hip ratio (WHR) than the MA and LS men, but MA and LS men differed only in waist circumference. Total and LDL-C levels were comparable, but HDL-C, HDL2-C, and %HDL2b subspecies were higher in MAs than in OS and LS men, and in LS than in OS men. Triglyceride (TG) was similar in MAs and LS men but higher in OS men. Across groups, two multiple regression analyses models (VO2max, %BF, and WHR or waist circumference) showed that %BF and VO2max independently predicted HDL-C and HDL2, whereas WHR predicted TG (r2 = .45) more strongly than waist circumference (r2 = .39). Postheparin lipoprotein lipase activity (LPL) was comparable among groups and correlated independently with VO2max. Total postheparin lipolytic activity (PHLA), hepatic lipase activity (HL), and HL:PHLA ratio were similar in MAs and LS men but higher in OS men. In both multiple regression analysis models, only %BF predicted HL activity and the HL:PHLA ratio. The HL:PHLA ratio independently predicted HDL-C, HDL2-C, %HDL2b, %HDL3 subspecies, and the cholesterol:HDL-C ratio, whereas LPL activity predicted TG. CONCLUSIONS: Increased fitness and reduced total and abdominal fatness in MAs are associated with lower HL and higher LPL activities, which may mediate their higher HDL-C and lower TG levels relative to their sedentary peers.     

Effects of two progestins with different androgenic properties on hepatic endothelial lipase and high density lipoprotein2

Thirty postmenopausal women were randomly treated with desogestrel (DG) or levonorgestrel (LN) 125 micrograms/day for 3 weeks. Desogestrel reduced the serum total and free (non-protein bound) testosterone concentrations. It caused a small decrease in the sex hormone binding globulin capacity (SHBG) but did not influence the free testosterone index (testosterone/SHBG ratio). Levonorgestrel, on the other hand, did not influence the free testosterone concentration, but caused a significant increase in the free testosterone index. Levonorgestrel reduced the HDL and particularly the HDL2 cholesterol concentrations (mean change from 1.75 to 1.45 mmol/l for HDL and from 0.73 to 0.50 mmol/l for HDL2, P less than 0.001). It also caused a reduction in the VLDL triglyceride (P less than 0.05) but not the total serum triglyceride concentration. Desogestrel did not cause any significant changes in HDL or HDL2 cholesterol concentrations, but it reduced the VLDL triglyceride (P less than 0.01) and total serum (P less than 0.05) triglyceride concentrations. Neither of the two progestins influenced the postheparin plasma lipoprotein lipase (LPL) activity or the serum cholesterol esterification rate by lecithin:cholesterol acyltransferase (LCAT). It is therefore possible that both steroids decreased the hepatic output of triglycerides, which may be clinically important since both progestins are used in combination with ethinylestradiol (EE) which increases the hepatic TG synthesis. The failure of desogestrel to change HDL levels is consistent with earlier data on the lack of effects on HDL by non-androgenic progestins. Levonorgestrel increased the mean activity of postheparin plasma hepatic lipase (HL) from 23.3 to 28.0 mumol X h-1 X ml-1 (P less than 0.05). In contrast, this activity was not influenced by desogestrel. The magnitude of the changes in postheparin plasma HL activity and the free testosterone index (testosterone/SHBG ratio) showed significant positive correlation (+ 0.41, P less than 0.05). On the other hand, the changes in the HDL2 cholesterol and the postheparin plasma HL activity were inversely interrelated (r = 0.52, P less than 0.01). These relationships are consistent with the idea that the effects of different progestins on the HDL cholesterol are mediated by the sex steroid sensitive hepatic endothelial lipase.     

Decreased activities of lipoprotein lipase and hepatic triglyceride lipase in patients with gout

Postheparin plasma lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) activities were measured in 30 male primary gout patients as well as in control subjects. The activities of these lipolytic enzymes were significantly decreased in the patients as compared with the controls (gout v control; LPL, 5.4 +/- 0.4 v 7.9 +/- 0.9 U; HTGL, 14.6 +/- 2.0 v 17.9 +/- 3.4 U) when matched with serum triglyceride concentration. Further, LPL activity was negatively correlated with serum- and very-low-density lipoprotein (VLDL)-triglyceride in gout patients, while that of HTGL was negatively correlated with low-density lipoprotein (LDL)-triglyceride in both gout patients and control subjects. These results suggest that decreased activities of LPL and HTGL may contribute, in part, to the increased concentrations of serum-, VLDL-, and LDL-triglyceride seen in gout patients, leading to a higher risk for coronary atherosclerotic diseases in gout.     

The effects of tolbutamide on lipoproteins, lipoprotein lipase and hormone-sensitive lipase

Type 2 diabetic patients are at increased risk to develop atherosclerotic vascular disease. These patients are often treated with sulphonylurea derivatives, and it has been suggested that this treatment might contribute to the increased atherosclerotic process. The aim of the present study was therefore to investigate whether tolbutamide influences lipid metabolism in such a way that the atherosclerotic process may be promoted. Addition of tolbutamide (5-500 mg/l) to isolated rat fat adipocytes inhibited the lipoprotein lipase (LPL) activity in a dose-dependent manner to levels about 50% of those registered in the absence of tolbutamide. This effect was due to inhibition of the activation of the enzyme in the tissue and not to interference with the interaction of enzyme with its substrate. Addition of tolbutamide (500 mg/l) also inhibited noradrenaline (100 nM) and isoprenaline (40 nM)-induced lipolysis by 48.1 +/- 7.4% (mean +/- S.E.M.) and 47.3 +/- 5.5%, respectively. The decreased lipolysis in tolbutamide preincubated adipocytes was shown to be the result of an inhibition of the phosphorylation of hormone sensitive lipase (HSL). Three months of tolbutamide treatment (0.5 g t.i.d.) in diet treated type 2 diabetic patients did not influence the plasma concentrations of cholesterol, triglycerides, LDL cholesterol, HDL cholesterol as well as HDL triglycerides and HDL phospholipids, and there were no differences compared to placebo treated patients. There was a tendency towards a decrement in the elimination rate of exogenous triglycerides in the tolbutamide group (P = 0.0801). No differences between the groups and no treatment effects were seen on LPL and hepatic lipase activities. In conclusion, our in vitro data show that tolbutamide has dual effects on lipid transport, with impairment of the LPL system, which would tend to decrease plasma lipoproteins by reducing hepatic production of lipoproteins. In vivo, these two effects seem to balance each other and plasma lipoprotein levels remain unaffected.     

Changes in serum lipids,lipoproteins, and heparin releasable lipolytic enzymes during moderate physical training in man: A longitudinal study

Serum lipids, postheparin plasma lipoprotein lipase (LPL) and hepatic lipase (HL) activity, and furthermore adipose tissue LPL activity were studied in 20 middle-aged men undergoing a moderate training program of 15-wk. These same parameters were also measured in 7 nontraining control subjects. The training caused a significant (P < 0.001) increase in physical fitness, and also considerable changes in serum lipid levels and lipolytic enzymes activities. In the trainers, serum HDL cholesterol increased by about 7% (P < 0.01) and HDL/total cholesterol ratio by 11% (P < 0.001). Decreases were observed in serum total (P < 0.10) and LDL (P < 0.05) cholesterol levels and in insulin values (P < 0.05). No changes in these parameters occurred in the reference group. Postheparin plasma and adipose tissue LPL activity increased by 33% (P < 0.001) and 56%, respectively, in the trainers. Postheparin plasma HL activity remained essentially the same in both groups, although a trend towards decreased values was seen in the trainers. On the other hand, postheparin plasma HL activity correlated negatively with serum HDL cholesterol levels both before and after the training period. The present results suggest that even with a moderate training program, beneficial effects on serum lipids in middle-aged men can be accomplished. There is also reason to believe that these changes are, at least in part, mediated by changes in the activities of lipolytic enzymes involved in lipoprotein metabolism, namely LPL and HL.