茶多酚对实验性动脉粥样硬化兔脂蛋白脂酶、肝脂酶活性的影响及意义

目的:观察动脉粥样硬化(AS)发生发展过程中脂蛋白脂酶(LPL)、肝脂酶(HL)活性的变化及茶多酚(TP)的作用。方法:高脂食物AS模型兔口服茶多酚200μg·g^-1·d^-1,测定血浆中LPL、HL活性,同时用组织化学法检测动脉壁层组织中LPL活性、肝组织中HL活性。结果:AS组动脉粥样硬化病变血管壁与正常对照组血管壁组织中LPL活性差异无显著(P＞0.05);AS组肝组织中HL活性明显低于正常对照组(P＜0.05)。TP组肝组织中HL活性明显高于AS组(P＜0.05)、血浆中TC和LDL-c水平低于AS组(P＜0.05)、动脉粥样硬化斑块面积低于AS组(P＜0.05)。各组间血浆LPL、HL活性水平差异无显著(P＞0.05)。结论:茶多酚能增加实验性AS兔肝组织中HL脂酶活性,这一作用与降低血浆胆固醇水平和抗动脉粥样硬化密切相关。     

Expression of type III hyperlipoproteinemia in patients homozygous for apolipoprotein E-2 is modulated by lipoprotein lipase and postprandial hyperinsulinemia

 Type III hyperlipoproteinemia (HLP) is a multifactorial disorder associated with homozygosity for the apolipoprotein (apo) E-2 allele. Factors which may promote the development of HLP include lipoprotein lipase (LPL) and hyperinsulinemia. These factors were investigated in eight patients with type III HLP and in nine normolipidemic controls. In vitro the interaction of apoE with LPL was analyzed in cell binding assays. All type III HLP patients showed delayed triglyceride (TG) clearance and remnant lipoprotein accumulation in an oral fat tolerance test. Normolipidemic apoE-2/2 controls revealed normal TG clearance comparable to apoE3/3 controls. HLP patients showed lower LPL activity and mass than controls. Analysis of the LPL gene revealed an Asn 291→Ser mutation in three patients and a –93 T-G substitution combined with an Asp 9→Asn mutation in one control subject. In addition to LPL abnormalities, postprandial hyperinsulinemia was observed in five out of eight patients. In vitro LPL compensated the defective function of apoE-2 in mediating remnant lipoprotein binding to cells. In summary, seven out of eight patients with type III HLP showed LPL abnormalities and/or postprandial hyperinsulinemia. Together with the in vitro data these findings support a coordinate effect of apoE and LPL for the manifestation of type III HLP. Hyperinsulinemia appears to be an additional factor important for disease expression. Received: 26 June 1997 / Accepted: 10 November 1997     

脂蛋白脂酶活性与早发冠心病临床表型关系的初步探讨

目的：探讨脂蛋白脂酶（LPL）活性与早发冠心病临床表型的关系。方法：测定106例早发冠心病患者（病例组）肝素化后血浆LPL活性，血脂参数和血浆C反应蛋白（CRP）浓度，与54例非冠心病者（对照组）进行比较；病例组按照患者临床表型分组，分析LPL活性特点。结果：病例组肝素化后血浆LPL活性低于对照组 [ (26.18±3.90) mmol·L^-1·min^-1 vs (35.27±5.96) mmol·L^-1·min^-1, P<0.05]，急性心肌梗死组LPL活性明显低于不稳定性心绞痛和稳定性心绞痛组。双因素相关分析，LPL与CRP呈显著负相关（r=-0.234，P<0.01）；多因素回归分析，低LPL活性可能是早发冠心病独立的危险因子（OR=6.32，95%CI 1.96-18.24，P<0.05)。结论：低LPL 活性是早发冠心病独立的危险因子，LPL活性与早发冠心病临床表型相关联。     

Lipoprotein lipase and hepatic triglyceride lipase reduce the infectivity of hepatitis C virus (HCV) through their catalytic activities on HCV-associated lipoproteins

The effect of lipolysis by lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) on hepatitis C virus (HCV) infection was evaluated. First, medium from HuH7.5 cells bearing HCV genome replication was treated with LPL. LPL treatment led to reduced HCV infectivity, shifted HCV to higher densities, and lowered the amount of apolipoprotein E-associated HCV. The effect of endogenous HTGL secreted from HuH7.5 on HCV infectivity was next examined. Neutralization of HTGL by an anti-HTGL antibody resulted in suppression of LPL-induced reduction in infectivity of HCV-bearing medium, while knockdown of HTGL by siRNA led to increased HCV infectivity irrespective of LPL. HCV in medium from HTGL knockdown cells was found in fractions with a lower density. These results indicate that changes in the nature of HCV-associated lipoproteins by LPL and/or HTGL affect HCV infectivity, suggesting that association of HCV with specific lipoproteins is important for HCV infectivity.     

Adipose tissue lipoprotein lipase (LPL) and triglyceride uptake in Zucker rats

To investigate the relationship between elevated adipose tissue lipoprotein lipase (LPL) activity and triglyceride uptake in Zucker obese rats, fed and 12 hour fasted female obese and lean Zucker rats were given intrajugular infusion of radio-labelled triglyceride and label clearance and uptake were examined over 35 minutes. In the fed state, obese rats showed more rapid clearance of the label from the bloodstream and, in both fed and fasted states, greater uptake into retroperitoneal and parametrical fat pads than lean rats. Obese rats showed proportionally less uptake into heart and liver. Regardless of feeding condition, obese rats exhibited elevations in adipose tissue LPL, which was significantly correlated with label uptake in adipose tissue. These results show that, in Zucker obese rats, elevated adipose tissue LPL is associated with increased adipose tissue triglyceride uptake. A preferential “shunting of calories” into adipose tissue, which is presumably mediated by LPL, could underlie the intractability of the Zucker obesity syndrome as well as the altered feeding behavior of Zucker obese rats.     

Adipose tissue lipoprotein lipase activity in rats maintained at a reduced body weight

Male rats fed a cellulose-diluted diet maintained a reduced body weight. Adipose tissue lipoprotein lipase (LPL) activity decreased after two days of cellulose feeding, but was not different from chow-fed control levels with weight stabilized at 90% or 70% of the control group. Plasma triglyceride concentration decreased with weight loss and remained depressed with stabilized reduced weight. Regaining lost weight had no effect on LPL activity when compared with chow-fed controls or with levels obtained for the weight-reduced group. However, plasma triglyceride concentration returned to chow-fed control levels with weight gain. The disparity between these results and those obtained in obese human beings lends support to the hypothesis that the increase in adipose tissue LPL activity in weight-reduced obese human beings is indicative of a defect in regulation of adipose tissue metabolism.     

Effects of low and moderate intensity treadmill walking on postprandial lipaemia in healthy young adults

We have previously shown that the lipaemic response to a fatty meal was reduced when prolonged (2 h) low intensity exercise was taken some hours before eating. The purpose of this study was to test the hypothesis that the effect is quantitatively greater after exercise of moderate intensity than after exercise at low intensity. Six men and six women, mean age 26.9 (SEM 1.5) years, took part in three trials, each conducted over 2 days; on the afternoon of day 1 of each of two exercise trials the subjects walked on a treadmill for 90 min at either 31 (SEM 1) % or 61 (SEM 1) % of maximal oxygen uptake, i.e. low and moderate intensity, respectively; on the control trial the subjects refrained from exercise on day 1. On the morning of day 2 of each trial they ingested a test meal (1.28 g fat, 1.44 g carbohydrate, 76 kJ energy · kg^–1 body mass); blood samples were obtained in the fasted state and for 6 h after the meal. Fasting serum triacylglycerol concentration and the area under the postprandial triacylglycerol-time curve were lower than in the control trial (P < 0.05) after moderate intensity walking but not after low intensity walking. The results suggest that the mitigation of the lipaemic response to a meal high in fat and carbohydrate is related to the intensity and/or the energy expenditure of the preceding exercise.     

Dietary effects on glycogen and lipoprotein lipase activity in skeletal muscle in man

The influence of short-term adaptation to a fat and protein enriched diet (F+P) and a carbohydrate enriched diet (CHO) on skeletal muscle lipoprotein lipase (LPL) activity and muscle glycogen levels was evaluated in 7 males. Muscle biopsies were taken from the m. vastus lateralis after an uncontrolled, mixed diet (M), after a 3 day F+P diet preceded by intense exercise, and after a 3 day CHO diet. After the F+P diet glycogen concentration was 55% that of the M diet while LPL activity increased by 21% (n. s.). After the CHO diet glycogen levels increased by 82% and LPL activity decreased by 55% compared to the M diet (p<0.01). The changes in LPL after the CHO diet were related to the changes in glycogen concentration (r = 0.98, p<0.01). LPL activity in the control situation was directly related to percent slow twitch (ST) muscle fibre type (r = 0.95, p<0.01). The results suggest that the uptake of fat from the circulation may be actively regulated by the muscle as a function of intramuscular substrate availability and that this regulation may be related to muscle fibre type composition.     

脂蛋白脂酶基因在子痫前期胎盘中的变化及意义

目的研究脂蛋白脂酶(lipoproteinlipase,LPL)mRNA在于痫前期患者胎盘组织中的表达与定位,探讨其在子痫前期病理生理过程中的作用。方法利用cDNA表达谱芯片检查子痫前期胎盘组织与正常胎盘组织之间的差异表达基因;根据筛选结果,采用半定量RT-PCR检测子痫前期患者胎盘组织(研究组)和正常孕妇胎盘组织(对照组)中LPLmRNA的表达;以原位杂交方法进行定位。结果在4轮杂交过程中,共筛选出22条有差异表达的基因,其中LPL基因为表达降低基因之一;正常胎盘组织和子痫前期胎盘组织中均存在LPLmRNA,子痫前期胎盘组织中LPLmRNA表达明显低于正常胎盘组织(0.208±0.067vs0.524±0.139,P<0.05);LPLmRNA分布在胎盘绒毛滋养细胞胞浆。结论胎盘组织中LPL的低表达可能参与子痫前期的发病过程。     

Glucose tolerance,plasma lipoproteins and tissue lipoprotein lipase activities in body builders

Summary Oral glucose tolerance, insulin binding to erythrocyte receptors, serum lipids, and lipoproteins, and lipoprotein lipase activities of adipose tissue and skeletal muscle were measured in nine body builders (relative body weight (RBW) 118±4%), eight weight-matched (RBW 120±5%) and seven normal-weight controls (RBW 111±3%). The body builders had 50% higher relative muscle mass of body weight (% muscle) and 50% smaller relative body fat content (% fat) than the two other groups (P<0.005). Maximal aerobic power was comparable in the three groups. In the oral glucose tolerance test (OGTT), blood glucose levels, and plasma insulin levels were lower (P<0.05) in the body builders than in weight-matched controls. Insulin binding to erythrocytes was similar in each group. On the basis of multiple linear regression analysis, 87% of the variation in plasma insulin response could be explained by body composition (% muscle and % fat) and .Plasma total cholesterol, low-density lipoprotein (LDL) cholesterol, and very low-density lipoprotein (VLDL) triglyceride concentrations were significantly lower in the body builders than in weight-matched controls. In comparison with the normal-weight group, the body builders had a lower total cholesterol level. High density lipoprotein (HDL) cholesterol, its subfractions (HDL₂ and HDL₃ cholesterol) and lipoprotein lipase (LPL) activities of adipose tissue and skeletal muscle were comparable in all three groups. Partial correlation analysis showed a positive relationship between plasma total triglyceride, total cholesterol and LDL cholesterol on the other hand and the % fat on the other.The results indicate that a shift in body composition from the adipose to the muscular type is associated with 1) lower glucose and insulin levels during the OGTT and 2) decrease in total and VLDL triglyceride and in total and LDL cholesterol levels but unchanged HDL cholesterol level. Thus, body builders are characterized by some metabolic features which decrease the risk of coronary heart disease. In contrast to aerobic training, body building does not influence HDL or its subfractions.     

妊高征与脂蛋白酯酶基因PvuⅡ多态性与血脂指标关系

目的探讨妊娠高血压综合征与脂蛋白酯酶(LPL)PvuII基因多态性的关系。方法运用多聚酶链反应-限制性内切酶片段长度多态性技术(PCR-RFLP)检测54例妊高征患者,100例正常妊娠妇女LPLPvuⅡ基因多态性。结果P+P+基因型血浆甘油三酶水平升高、HDL-c水平降低,与P+P-基因型、P-P-基因型比较,差异有统计学意义(P=0.000和P=0.001),提示P+P+基因型可引起血浆TG升高、HDL-c降低。妊高征组和对照组不同基因型间血浆TG、LDL-c差异无统计学意义。3种基因型频率与对照组相比差异无统计学意义。结论PvuⅡ突变可能不是构成妊高征的独立遗传性危险因子。     

Recurrent missense mutations at the first and second base of codon Arg243 in human lipoprotein lipase in patients of different ancestries

Mutations in the lipoprotein lipase (LPL) gene are the most common cause of familial chylomicronemia. Here we define the molecular basis of LPL deficiency in four patients of German, French, Dutch, and Chinese descent. We show that two of the probands of Dutch and Chinese origin have a previously described Arg²⁴³His mutation while the patients of German and French descent have a novel Arg²⁴³ Cys substitution in their LPL gene. Haplotype analysis is in favour of two separate origins for the Arg²⁴³ Cys substitution which together with the Arg²⁴³ His mutation would implicate three recurrent mutations involving the first and second nuclcotides of the codon encoding Arg²⁴³ of the LPL gene. The recurrent mutations affecting the first and second nucleotide of CGC coding for the normal Arg residue are support for the high mutability of CpG dinucleotides within the LPL gene. © 1994 Wiley-Liss, Inc.     

Ovarian modulation of lipoprotein lipase activity in white adipose tissue of ground squirrels

Golden-mantled ground squirrels were ovariectomized (OVX) or Sham-OVX during the weight gain phase of the circannual body weight cycle. Other squirrels, OVX or Sham-OVX during the weight loss phase, were subcutaneously implanted with estradiol-filled or empty Silastic capsules. The mass of several fat pads as well as adipose tissue lipoprotein lipase (LPL) activity were determined at autopsy. Ovariectomy at either phase of the annual cycle was without effect on body weight. However, LPL activity of the parametrial fat pad was increased in OVX as compared to Sham-OVX squirrels. Fourteen days of estradiol treatment during the weight loss phase decreased the mass and LPL activity of the retroperitoneal fat depot but did not affect these parameters in perirenal adipose tissue. Although estradiol exerts different or opposite effects on body mass and food intake of rats and ground squirrels, ovariectomy and estrogen treatment affect LPL activity in a similar fashion in both species.     

Food intake and adipose tissue lipoprotein lipase activity after hypothalamic estradiol benzoate implants in rats

Unilateral implants of estradiol benzoate in the ventromedial hypothalamus (VMH) reduced food intake in ovariectomized rats. The implants did not produce cornification of the vaginal epithelium. Furthermore, the reduction in food intake was observed in the absence of changes in adipose tissue lipoprotein lipase activity or cytoplasmic progestin receptor levels. These results suggest that, while estradiol may normally act at both central and peripheral sites to affect food intake and body weight, estrogenic stimulation of just the VMH may be sufficient to reduce food intake in ovariectomized rats.     

Exercise-induced changes in lipoprotein lipase activity (LPLA) in skeletal muscles of the dog

The aim of this work was to study the effect of physical exercise on muscle lipoprotein lipase activity (LPL) in dogs. Existence of two forms of LPL: heparin releasable and unreleasable was demonstrated in skeletal muscles, and the changes in the activity of both forms were followed during 3 h treadmill running, using biopsy samples taken from m. biceps femoris.During the first two hours of exercie the heparin releasable form of LPL was progressively increasing, whereas the heparin unreleasable form of the enzyme was decreasing. Thus, a significant negative correlation between activities of the two forms was ascertained (r=0.72,P<0.01). In the final period of exercise, activity of the heparin releasable form of LPL tended to stabilize on the enhanced level, and activity of the heparin unreleasable form increased.In the further series of experiments a relationship between exercise intensity and activity of the heparin releasable form of LPL was studied during 1 h exercise bouts.A significant positive correlation (r=0.84,P<0.001) was ascertained between LPL activity and intensity of work. A comparison between LPL activity in the muscle engaged in exercise (m. biceps femoris) and nonactive muscle (m. coccygeus) revealed that the enhancement of the enzyme activity during physical work does not occur in the latter.In conclusion: it was found that physical exercise induces a marked intensity-dependent increase of LPL activity in working muscles, which is probably caused by an elevated transport of the enzyme molecules from the muscle cells to the intravascular space. The latter suggestion is based on the reciprocal changes of the heparin releasable and unreleasable (probably intracellular) forms of LPL.This work was supported by the Polish Academy of Sciences within the project 10.4.     

The effect of acute aerobic exercise on pulse wave velocity and oxidative stress following postprandial hypertriglyceridemia in healthy men

Oxidative stress is postulated to be responsible for the postprandial impairments in vascular function. The purpose of this study was to measure pulse wave velocity (PWV) and markers of postprandial oxidative stress before and after an acute bout of moderate exercise. Ten trained male subjects (age 21.5 ± 2.5 years, VO₂ max 58.5 ± 7.1 ml kg⁻¹ min⁻¹) participated in a randomised crossover design: (1) high-fat meal alone (2) high-fat meal followed 2 h later by a bout of 1 h moderate (60% max HR) exercise. PWV was examined at baseline, 1, 2, 3, and 4 h postprandially. Blood Lipid hydroperoxides (LOOHs), Superoxide dismutase (SOD) and other biochemical markers were measured. PWV increased at 1 h (6.49 ± 2.1 m s⁻¹), 2 h (6.94 ± 2.4 m s⁻¹), 3 h (7.25 ± 2.1 m s⁻¹) and 4 h (7.41 ± 2.5 m s⁻¹) respectively, in the control trial (P < 0.05). There was no change in PWV at 3 h (5.36 ± 1.1 m s⁻¹) or 4 h (5.95 ± 2.3 m s⁻¹) post ingestion in the exercise trial (P > 0.05). LOOH levels decreased at 3 h post ingestion in the exercise trial compared to levels at 3 h (P < 0.05) in the control trial. SOD levels were lower at 3 h post ingestion in the control trial compared to 3 h in the exercise trial (0.52 ± 0.05 vs. 0.41 ± 0.1 units μl⁻¹; P < 0.05). These findings suggest that a single session of aerobic exercise can ameliorate the postprandial impairments in arterial function by possibly reducing oxidative stress levels.     

Physical activity modulates the effect of a lipoprotein lipase mutation (D9N) on plasma lipids and lipoproteins

We investigated interactions between a mutation (D9N) in the lipoprotein lipase (LPL) gene and physical activity, as well as other lifestyle factors, on lipid traits in a population-based sample of Dutch men and women (n = 379). We used questionnaire information to classify physical activity, alcohol consumption, and smoking habits, while overweight was defined as a body mass index (BMI) > 25 kg/m2. Non-fasting blood samples were used for the determination of lipid traits and the D9N genotype. Fifteen subjects (4%) carried the mutation. They presented with higher levels of total cholesterol, apolipoprotein (apo) B and triglycerides compared to non-carriers. While no interactions with overweight, alcohol consumption, and smoking were found, a strong interaction between the D9N mutation and physical activity became apparent. Physically inactive D9N carriers (n = 5) had considerably higher total cholesterol (+2 mmol/l, p < or = 0.0001) and apo B levels (+63 mg/dl, p < or = 0.0001) compared to non-carriers of this mutation, whereas their high-density lipoprotein (HDL)-cholesterol concentrations were lower (-0.22 mmol/l, p < 0.05). This was not the case for physically active D9N carriers (n = 10). In conclusion, a common variant of the LPL gene (D9N) adversely affects plasma lipid and lipoprotein profiles. However, the unfavorable consequences may be counteracted by physical activity.