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PubMed1980

Post-heparin plasma lipoprotein and hepatic lipases. Relationships to high density lipoprotein cholesterol and to apolipoprotein CII in familial hyperalphalipoproteinemic and in normal subjects.

Post-heparin lipoprotein lipase (PH-LPL)-high density lipoprotein cholesterol (HDL-C) interrrelationships were assessed in 9 subjects with documented familial hyperalphalipoproteinemia (FHA) and in 8 controls to focus on potential biochemical etiologies of FHA and relationships of HDL-C to triglyceride hydrolysis and PH-LPL. FHA subjects had mean HDL-C and HDL2-C levels > twice controls; their PH-LPL levels (mean +/- SEM) (3.14 +/- 2.3 mumol FFA/h/ml) were also > twice that of controls (15.0 +/- 1.6) (P < 0.01), but post-heparin hepatic lipase levels (PH-HL) in the FHA and control subjects did not differ (18.1 +/- 1.6 vs 26.6 +/- 4.3, P > 0.1). For all subjects (FHA and controls) PH-LPL was positively correlated with HDL-C (r = 0.79, P < 0.01) and with HDL2-C (r = 0.90, P < 0.01), but not with HDL3-C (r = --0.02). There were no significant PH-HL and HDL-C interrelationships, P > 0.1. The amount of apo CII (the primary activator of PH-LPL) in HDL2 was greater in the FHA (mean +/- SEM) (16.1 +/- 2.5 microgram/ml plasma) than in control subjects (4.7 +/- 0.9, P < 0.01). There were strong positive correlations between HDL2 apo CII and both PH-LPL (r = 0.79, P < 0.01) and HDL2-C (r = 0.80, P < 0.01). Apo CII as a percentage of HDL2 protein was higher in FHA than control subjects (mean +/- SEM) (1.2 +/- 0.3% vs 0.5 +/- 0.2%, P < 0.01). Apo CII as a percentage of HDL3 protein was similar in FHA and control subjects. We postulate that increased turnover rate of triglyceride-rich lipoproteins due to high LPL activity may be an important factor leading to the elevation of HDL-C in FHA. The highly significant positive correlation between HDL2-C and PH-LPL provides strong clinical evidence for the theory that HDL2 is formed during the hydrolysis of triglycceride-rich lipoproteins. The high concentration of HDL2 apo CII in FHA subjects may be caused by increased catabolism of triglyceride-rich lipoproteins in the presence of high endothelial LPL, with transfer of apo CII from very low to high density lipoproteins.

Adolescent↗

PubMed1983

Circulating triacylglycerols, lipoproteins, and tissue lipoprotein lipase activities in rat mothers and offspring during the perinatal period: effect of postmaturity.

Mammary gland and adipose tissue lipoprotein lipase activities have been implicated in the changes of circulating triacylglycerol levels which occur in the mother at late gestation. In the newborn the temporal accumulation of triacylglycerols in the liver coincides with the appearance of a lipoprotein lipase peak. The relationships of these changes with the rise in circulating prolactin in the mother before parturition and the extrauterine nutritional status in the offspring were studied in a postmaturity model produced in the rat by subcutaneous injection of 7 mg progesterone/day to pregnant animals from the 20th day of gestation. Pregnant controls received the medium. Parturition occurred at day 21.5 of gestation in pregnant controls while it did not occur before the 23rd day in those receiving progesterone. At the 20th day of gestation, plasma triacylglycerol concentrations and all lipoprotein fractions (especially VLDL) were much higher in mothers not receiving progesterone than in age-matched virgins, and these differences disappeared at the 21st day of gestation. Lipoprotein lipase activity was maintained low in control mothers' adipose tissue until the 23rd postfecundation day while it greatly increased in mammary gland from parturition time. In progesterone treated mothers, both triacylglycerol and lipoprotein fractions (especially VLDL) in plasma were maintained elevated until the 23rd postfecundation day and adipose tissue and mammary gland lipoprotein lipase activities were maintained low until this time.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Does lipoprotein or hepatic lipase activity explain the protective lipoprotein profile of premenopausal women?

Numerous studies have reported that women have a lipoprotein profile suggestive of a reduced risk of coronary heart disease (CHD). We have therefore tested whether the "protective" lipoprotein profile of women could be explained by differences in hepatic lipase (HL) or lipoprotein lipase (LPL) activities. In the present study, 14 non-obese healthy premenopausal women had higher plasma concentrations of high-density lipoprotein cholesterol (HDL-C), HDL2-C, HDL3-C, and HDL-apolipoprotein (apo) AI, and a higher ratio of HDL-C to low-density lipoprotein cholesterol (LDL-C) than 17 non-obese healthy men. Women also had lower plasma triglyceride (TG), HDL-TG, and apo B levels than men. Plasma postheparin LPL (PH-LPL) and HL activities showed no significant sex dimorphism, whereas abdominal and femoral adipose tissue (AT)-LPL activities were significantly higher in women (P < .005). In men, PH-LPL activity correlated significantly with plasma HDL2-C (r = .52, P < .05), LDL-C (r = -.47, P < .05), and apo B (r = -.56, P < .01) levels, as well as with the HDL-C/LDL-C ratio (r = .67, P < .005). No such relationships were found in women, with the exception of HL activity, which was negatively correlated with HDL-apo AI levels. In both genders, abdominal AT-LPL activity showed no significant association with plasma lipoprotein levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed2001

The atherogenic lipoprotein phenotype: small dense LDL and lipoprotein remnants in nephrotic range proteinuria.

The dyslipidaemia in nephrotic-range proteinuria is believed to contribute to the increased atherogenesis associated with the condition. Excess small dense low density lipoprotein (LDLIII) contributes to this risk. Lipoprotein remnants (RLP) may also be implicated but have not been studied in this population. We measured the plasma concentration of low density lipoprotein (LDL) subfractions (by density gradient ultracentrifugation), RLP (by immunoaffinity gel), very low density lipoprotein (VLDL) subfractions, post heparin lipases and cholesteryl ester transfer protein (CETP) activity in 27 patients with glomerular disease and albuminuria >2.0g. These were compared with 27 age and sex matched controls. Proteinuric patients had increased LDLIII concentration (patients 182 (84:267) vs. controls 31 (27:62); P<0.0001) with reduced lighter LDLI (36 (24:43) vs 69 (46:101); P<0.0005) and LDLII (124 (79:220) vs 178 (129:236); P<0.04, all mg/dl, median+interquartile range). RLP-cholesterol (RLP-C) and triglyceride (RLP-TG) were increased in proteinuric patients (RLP-C 18.9 (11.0:26.9) vs 7.7 (6.0:8.8); P<0.0001, RLP-TG 35.8 (11.8:54.7) vs. 7.2 (4.3:10.0); P<0.0001, all mg/dl). Increased LDLIII and RLP were independent of renal function. VLDL(1) and VLDL(2) concentrations were increased by 258 and 260% (both P<0.0001). CETP activity was increased by 46% (P<0.005). Lipoprotein and hepatic lipase activities did not differ from control values. LDLIII concentration (r(2)=45.7%, P<0.001), RLP-C (r(2)=85.2%, P<0.001) and RLP-TG (r(2)=87.5%, P<0.001) all correlated positively with plasma triglyceride. Moreover, increased LDLIII was associated with both RLP-C (r(2)=31.3%, P<0.002) and RLP-TG (r(2)=33.6%, P<0.002). Excess LDLIII and RLP are present in nephrotic-range proteinuria and add to the spectrum of cardiovascular risk factors present in proteinuric patients. Increases in LDLIII and RLP are closely related to plasma triglyceride. The association between excess RLP and LDLIII suggests that RLP contribute to the increased atherogenicity attributed to the atherogenic lipoprotein phenotype.

Adult↗

PubMed1994

Epidemiology of triglycerides, small dense low-density lipoprotein, and lipoprotein(a) as risk factors for coronary heart disease.

In addition to LDL cholesterol, triglyceride; small, dense LDL (LDL subclass phenotype B); and lipoprotein(a) are emerging as important risk factors for CHD. Elevated plasma levels of each of these risk factors have consistently been associated with increased risk of CHD in case-control studies of white patients. In prospective studies, however, the association between triglycerides and CHD is generally not independent of HDL cholesterol in multivariate statistical analyses. Although the data are scarce, studies in women show that triglycerides are a stronger risk factor for CHD in women than in men. Although no prospective studies of LDL subclass phenotype B have been reported, a number of potential atherogenic mechanisms may be responsible for the association with CHD seen in the case-control studies. Similarly, few prospective studies of lipoprotein(a) have been published, all in Scandinavian men. The observational studies generally show an association between elevated lipoprotein(a) and CHD in whites but not in blacks. Each of these risk factors also has a genetic component. Of the two familial forms of hypertriglyceridemia, FCH has been associated with familial CHD in two cross-sectional studies. LDL subclass phenotype B is inherited consistent with a single major gene effect, and candidate gene linkage studies are in progress to map the chromosomal location of this proposed gene. Finally, lipoprotein(a) levels are largely attributable to variation at the apo(a) locus on chromosome 6. Whether other genetic variations explain the lack of reported associations between lipoprotein(a) and CHD in black populations remains to be determined. Understanding of these "non-LDL" lipoprotein-related risk factors will provide important information for the development of new, effective intervention strategies for the prevention of CHD.

Arteriosclerosis↗

PubMed1997

Influence of fitness status on very-low-density lipoprotein subfractions and lipoprotein(a) in men and women.

The purpose of this study was to examine the influence of the physical activity level of men and women on the very-low-density lipoprotein (VLDL) subfractions and lipoprotein(a) [Lp(a)]. Fifty-four men (n = 30) and women (n = 24) aged 30 to 53 years were recruited based on their level of activity over the past 2 years, and formed three groups: sedentary (S), no routine activity; recreational exercise (R), routine moderate exercise three to five times per week; and trained (T), competition-based, high-volume aerobic training five to seven times per week. Each subject underwent a maximal oxygen consumption (VO2max) test and was measured for body composition (skinfolds) and waist to hip ratio (WHR). Following a prescribed 24-hour diet and abstinence from activity, a blood sample was obtained from each subject and the plasma was analyzed for cholesterol and triglycerides (TGs) in VLDL1, VLDL2, and VLDL3 subfractions. High-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and Lp(a) also were analyzed. Total VLDL-C was higher in men than in women, but no gender differences were observed in VLDL subfractions. VLDL1-TG and VLDL2-TG were elevated in the S group compared with groups R and T, even though total VLDL-TG, LDL-C, and HDL-C values were not different among the groups. Values for Lp(a) were not significantly different between men and women or among the groups. The two exercising groups were not different on any lipoprotein variable or WHR. VLDL1-TG was inversely correlated with VO2max and HDL-C. These results suggest that life-style activity is associated with a favorable VLDL subfraction pattern and WHR, but not Lp(a). In addition, long-term recreational activity is associated with a lipoprotein profile and WHR similar to those obtained with higher-volume exercise training.

Adult↗

PubMed1999

Interrelationships between postprandial lipoprotein B:CIII particle changes and high-density lipoprotein subpopulation profiles in mixed hyperlipoproteinemia.

We studied the relationships postprandially between triglyceride-rich lipoprotein (TRL) and high-density lipoprotein (HDL) in 11 mixed hyperlipoproteinemia (MHL) and 11 hypercholesterolemia (HCL) patients. The high and prolonged postprandial triglyceridemia response observed in MHL but not HCL patients was essentially dependent on very-low-density lipoprotein (VLDL) changes. This abnormal response was related to decreased lipoprotein lipase (LPL) activity (-48.7%, P<.01) in MHL compared with HCL subjects. Cholesteryl ester transfer protein (CETP) activity was postprandially enhanced only in MHL patients, and this elevation persisted in the late period (+19% at 12 hours, P<.05), sustaining the delayed enrichment of VLDL with cholesteryl ester (CE). The late postprandial period in MHL patients was also characterized by high levels of apolipoprotein B (apoB)-containing lipoproteins with apoCIII ([LpB:CIII] +36% at 12 hours, P<.01) and decreased levels of apoCIII contained in HDL ([LpCIII-HDL] -34% at 12 hours, P<.01), reflecting probably a defective return of apoCIII from TRL toward HDL. In MHL compared with HCL patients, decreased HDL2 levels were related to both HDL2b and HDL2a subpopulations (-57% and -49%, respectively, P<.01 for both) and decreased apoA-I levels (-53%, P<.01) were equally linked to decreased HDL2 with apoA-I only (LpA-I) and HDL2 with both apoA-I and apoA-II ([LpA-I:A-II] -55% and -52%, respectively, P<.01 for both). The significant inverse correlations between the postprandial magnitude of LpB:CIII and HDL2-LpA-I and HDL2b levels in MHL patients underline the close TRL-HDL interrelationships. Our findings indicate that TRL and HDL abnormalities evidenced at fasting were postprandially amplified, tightly interrelated, and persistent during the late fed period in mixed hyperlipidemia. Thus, these fasting abnormalities are likely postprandially originated and may constitute proatherogenic lipoprotein disorders additional to the HCL in MHL patients.

Adult↗

PubMed2000

Lipoprotein profiles, not anthropometric measures, correlate with serum lipoprotein(a) values in children: the Taipei children heart study.

OBJECTIVE: Plasma lipoprotein(a) [Lp(a)] is a risk factor for cardiovascular disease. The purpose of this study is to evaluate the correlation of anthropometric measures, lipids and lipoprotein profiles and serum Lp(a) values among children in Taiwan. We will attempt to find parameters that will be able to predict Lp(a) levels in children. DESIGN AND METHODS: After a probability-proportional-to size, multi-stages sampling procedure, we randomly sampled 1500 schoolchildren from 10 schools in Taipei city. Anthropometric measures including body weight, body height, waist and hip circumference and skinfolds were measured. We used standard methods to measure serum total cholesterol (CHOL), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), apolipoprotein A1 and B (ApoA1 and ApoB) and Lp(a) levels. We also calculated low density lipoprotein-cholesterol (LDL-C) and CHOL HDL-C ratio (TCHR) by formula. RESULTS: We sampled 1283 children (635 boys and 648 girls) with a mean age of 13.3 years (from 12 to 16 years) in this study. The mean and medium serum Lp(a) levels were 16.8 and 8.8 mg/dl among boys and 20.8 and 11.9 mg/dl among girls. Children in the highest quintile of Lp(a) (mean = 49.6 and 58.6 mg/dl for boys and girls, respectively) had higher CHOL, LDL-C, ApoB levels and TCHR than children in the lowest quintile (mean = 3.1 and 3.7 mg/dl for boys and girls, respectively). Lipids and lipoprotein profiles, such as CHOL, LDL-C, Apo-B and TCHR were positively correlated with Lp(a) levels in both genders. Furthermore, the children with Lp(a) levels greater than or equal to 30 mg/dl had higher CHOL, LDL-C and Apo-B levels when compared to children with Lp(a) levels less than 30 mg/dl. After adjusting for age, cigarette smoking, alcohol drinking, puberty development and heart rates, LDL-C and ApoB levels were significantly positively associated with Lp(a) levels while ApoA1 was negatively associated among boys. Among girls, only Apo-B was significantly positively associated with Lp(a) and TG was negatively associated with Lp(a) levels. Most importantly, none of the anthropometric measures were significantly correlated with Lp(a) levels. CONCLUSIONS: From this study, we found that lipids and lipoproteins profiles, rather than degree of adiposity as reflected by anthropometric measures, are significantly associated with serum Lp(a) levels among school children.

Adolescent↗

PubMed1996

Lipoprotein lipase stimulates the binding and uptake of moderately oxidized low-density lipoprotein by J774 macrophages.

Lipoprotein lipase (LPL) stimulates the uptake of low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) in different cell types, including macrophages, through bridging of LPL between lipoproteins and extracellular heparan sulphate proteoglycans (HSPG). Because macrophages produce LPL and because modified lipoproteins are present in the arterial wall in vivo, we wondered whether LPL also enhances the uptake of oxidized LDL by J774 macrophages. LDL samples with different degrees of oxidation, as evaluated by relative electrophoretic mobility (REM) as compared with native LDL are used as well as native and acetylated LDL. Addition of 5 microg/ml LPL to the J774 cell culture medium stimulated the binding of both native LDL and moderately oxidized LDL (REM < 3.5) 50-100-fold, and their uptake was stimulated approx. 20-fold. The LPL-mediated binding of native LDL and moderately oxidized LDL was dose-dependent. Preincubation of the cells with heparinase (2.4 units/ml) inhibited the stimulatory effect of LPL, indicating that this LPL-mediated stimulation was due to bridging between the lipoproteins and HSPG. The binding to J774 macrophages of severely oxidized LDL (REM=4.3) was stimulated less than 3-fold by LPL, whereas its uptake was not stimulated significantly. The binding and uptake of acetylated LDL (AcLDL) were not stimulated by LPL, although the LPL-molecule itself does bind to AcLDL. Measurements of the cellular lipid content showed that addition of LPL also stimulated the accumulation in the cells of cholesteryl ester derived from both native LDL and moderately oxidized LDL in a dose-dependent manner. We conclude that our results present experimental evidence for the hypothesis that LPL serves as an atherogenic component in the vessel wall.

Acetylation↗

PubMed1996

Molecular characterization of quail apolipoprotein very-low-density lipoprotein II: disulphide-bond-mediated dimerization is not essential for inhibition of lipoprotein lipase.

As part of the avian reproductive effort, large quantities of triglyceride-rich very-low-density lipoprotein (VLDL) particles are transported by receptor-mediated endocytosis into the female germ cells. Although the oocytes are surrounded by a layer of granulosa cells harbouring high levels of active lipoprotein lipase, non-lipolysed VLDL is transported into the yolk. This is because VLDL particles from laying chickens are protected from lipolysis by apolipoprotein (apo)-VLDL-II, a potent dimeric lipoprotein lipase inhibitor [Schneider, Carroll, Severson and Nimpf (1990) J. Lipid Res. 31, 507-513]. To determine whether this protection depends on dimer formation and constitutes a general mechanism to ensure high levels of yolk triglycerides for embryonic utilization in birds, we have now molecularly characterized apo-VLDL-II in the Japanese quail, a frequently used avian species. Quail apo-VLDL-II shows 72% amino acid identity with the chicken protein, with most replacements being in the C-terminal region. Importantly, quail apo-VLDL-II lacks the single cysteine residue present eight residues from the C-terminus of chicken apo-VLDL-II, which is responsible for dimerization of the chicken lipoprotein lipase inhibitor. Nevertheless, monomeric quail and dimeric chicken apo-VLDL-II display, on a molar basis, identical inhibitory effects on lipoprotein lipase, underscoring the biological importance of their function. Furthermore secondary structure prediction of the 3'-untranslated region of the quail message supports a role for loop structures in the strictly oestrogen-dependent production of the lipoprotein lipase inhibitors. Our findings shed new light on the essential role of this small, hormonally regulated, protein in avian reproduction.

Amino Acid Sequence↗

PubMed2000

Variation of lipids and lipoproteins in premenopausal women compared with men and postmenopausal women. DELTA (Dietary Effects on Lipoproteins and Thrombogenic Activity) Investigators.

Numerous studies have reported cyclic fluctuations in lipids and lipoproteins as a function of the phase of the menstrual cycle. However, the reported patterns are quite variable and have led to an unclear picture of the influence of the menstrual cycle on the variability of lipids, and hence of the role of the menstrual cycle phase in the interpretation of serum lipids for premenopausal women. As part of the DELTA Study (Dietary Effects on Lipoproteins and Thrombogenic Activity), we evaluated the cyclic variation of circulating lipids and lipoproteins in 39 premenopausal women and compared intraindividual variances in these women, 18 postmenopausal women, and 46 men under conditions of tight dietary control. Cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, apolipoproteins A-1 (apo A-1) and B-100 (apo B-100), and lipoprotein (a) [Lp(a)] all demonstrated cycling in the premenopausal women. However, the observed cycling accounts for only a small fraction of the total biologic variability of lipids in premenopausal women. The magnitude of total intraindividual variability based on coefficient of variation (CV) for these lipids in premenopausal women (CV, 4% to 8.1%) was similar to that found for men (CV, 4.3% to 9.1%) and for postmenopausal women (CV, 3.7% to 6.7%). These results suggest that protocols for screening and monitoring of serum lipids in premenopausal women need not differ from those used for men or postmenopausal women.

Adult↗

PubMed1984

Role of apolipoprotein E in the lipolytic conversion of beta-very low density lipoproteins to low density lipoproteins in type III hyperlipoproteinemia.

The beta-very low density lipoproteins (beta-VLDL) that accumulate in type III hyperlipoproteinemic subjects can be divided into two fractions (fraction I and fraction II), which differ in size, lipid composition, and the type of apolipoprotein B (apo-B) present in the particles. The apo-B48-containing particles (fraction I) are of intestinal origin, while apo-B100-containing particles (fraction II) are derived from the liver. Both fractions contain a defective form of apo-E referred to as apo-E2. Intravenous infusion of heparin into two subjects with type III hyperlipoproteinemia resulted in the complete removal of fraction II particles from density less than 1.006 g/ml, while fraction I particles remained at this density. In vitro studies confirmed that fraction I particles did not change density when subjected to hydrolysis with lipoprotein lipase, while fraction II particles shifted to the intermediate density lipoprotein range (approximately equal to 1.02 g/ml). When the beta-VLDL were hydrolyzed by lipoprotein lipase in the presence of density greater than 1.21 g/ml lipoprotein-deficient plasma, the addition of normal apo-E (apo-E3), but not apo-E2, resulted in a shift of fraction II particles to the low density lipoprotein (LDL) range (approximately equal to 1.05 g/ml). Fraction I particles did not undergo a shift to this higher density, supporting previous observations that apo-B48-containing particles are not converted to LDL. The demonstration that apo-B100-containing particles in type III hyperlipoproteinemic subjects could be converted to particles with the density of LDL suggests that apo-E plays a role in the normal conversion of VLDL to LDL. The mutant form of apo-E (apo-E2) found in the beta-VLDL from type III hyperlipoproteinemic subjects appears to impede this conversion, whereas the addition of normal apo-E (apo-E3) allows the processing to occur.

Animals↗

PubMed2001

Binding of low density lipoproteins to lipoprotein lipase is dependent on lipids but not on apolipoprotein B.

Lipoprotein lipase (LPL) efficiently mediates the binding of lipoprotein particles to lipoprotein receptors and to proteoglycans at cell surfaces and in the extracellular matrix. It has been proposed that LPL increases the retention of atherogenic lipoproteins in the vessel wall and mediates the uptake of lipoproteins in cells, thereby promoting lipid accumulation and plaque formation. We investigated the interaction between LPL and low density lipoproteins (LDLs) with special reference to the protein-protein interaction between LPL and apolipoprotein B (apoB). Chemical modification of lysines and arginines in apoB or mutation of its main proteoglycan binding site did not abolish the interaction of LDL with LPL as shown by surface plasmon resonance (SPR) and by experiments with THP-I macrophages. Recombinant LDL with either apoB100 or apoB48 bound with similar affinity. In contrast, partial delipidation of LDL markedly decreased binding to LPL. In cell culture experiments, phosphatidylcholine-containing liposomes competed efficiently with LDL for binding to LPL. Each LDL particle bound several (up to 15) LPL dimers as determined by SPR and by experiments with THP-I macrophages. A recombinant NH(2)-terminal fragment of apoB (apoB17) bound with low affinity to LPL as shown by SPR, but this interaction was completely abolished by partial delipidation of apoB17. We conclude that the LPL-apoB interaction is not significant in bridging LDL to cell surfaces and matrix components; the main interaction is between LPL and the LDL lipids.

Animals↗

PubMed2001

Inactive lipoprotein lipase (LPL) alone increases selective cholesterol ester uptake in vivo, whereas in the presence of active LPL it also increases triglyceride hydrolysis and whole particle lipoprotein uptake.

We have previously shown that transgenic expression of catalytically inactive lipoprotein lipase (LPL) in muscle (Mck-N-LPL) enhances triglyceride hydrolysis as well as whole particle lipoprotein and selective cholesterol ester uptake. In the current study, we have examined whether these functions can be performed by inactive LPL alone or require the presence of active LPL expressed in the same tissue. To study inactive LPL in the presence of active LPL in the same tissue, the Mck-N-LPL transgene was bred onto the heterozygous LPL-deficient (LPL1) background. At 18 h of age, Mck-N-LPL reduced triglycerides by 35% and markedly increased muscle lipid droplets. In adult mice, it reduced triglycerides by 40% and increased lipoprotein particle uptake into muscle by 60% and cholesterol ester uptake by 110%. To study inactive LPL alone, the Mck-N-LPL transgene was bred onto the LPL-deficient (LPL0) background. These mice die at approximately 24 h of age. At 18 h of age, in the absence of active LPL, inactive LPL expression did not diminish triglycerides nor did it result in the accumulation of muscle lipid droplets. To study inactive LPL in the absence of active LPL in the same tissue in adult animals, the Mck-N-LPL transgene was bred onto mice that only expressed active LPL in the heart (LPL0/He-LPL). In this case, Mck-N-LPL did not reduce triglycerides or increase the uptake of lipoprotein particles but did increase muscle uptake of chylomicron and very low density lipoprotein cholesterol ester by 40%. Thus, in the presence of active LPL in the same tissue, inactive LPL augments triglyceride hydrolysis and increases whole particle triglyceride-rich lipoprotein and selective cholesterol ester uptake. In the absence of active LPL in the same tissue, inactive LPL only mediates selective cholesterol ester uptake.

Animals↗

PubMed2004

The peroxisome proliferator-activated receptor alpha (PPARalpha) agonist ciprofibrate inhibits apolipoprotein B mRNA editing in low density lipoprotein receptor-deficient mice: effects on plasma lipoproteins and the development of atherosclerotic lesions.

Low density lipoprotein receptor (LDLR)-deficient mice fed a chow diet have a mild hypercholesterolemia caused by the abnormal accumulation in the plasma of apolipoprotein B (apoB)-100- and apoB-48-carrying intermediate density lipoproteins (IDL) and low density lipoproteins (LDL). Treatment of LDLR-deficient mice with ciprofibrate caused a marked decrease in plasma apoB-48-carrying IDL and LDL but at the same time caused a large accumulation of triglyceride-depleted apoB-100-carrying IDL and LDL, resulting in a significant increase in plasma cholesterol levels. These plasma lipoprotein changes were associated with an increase in the hepatic secretion of apoB-100-carrying very low density lipoproteins (VLDL) and a decrease in the secretion of apoB-48-carrying VLDL, accompanied by a significant decrease in hepatic apoB mRNA editing. Hepatic apobec-1 complementation factor mRNA and protein abundance were significantly decreased, whereas apobec-1 mRNA and protein abundance remained unchanged. No changes in apoB mRNA editing occurred in the intestine of the treated animals. After 150 days of treatment with ciprofibrate, consistent with the increased plasma accumulation of apoB-100-carrying IDL and LDL, the LDLR-deficient mice displayed severe atherosclerotic lesions in the aorta. These findings demonstrate that ciprofibrate treatment decreases hepatic apoB mRNA editing and alters the pattern of hepatic lipoprotein secretion toward apoB-100-associated VLDL, changes that in turn lead to increased atherosclerosis.

Animals↗

PubMed1991

Changes in lipoprotein metabolism and body composition in chickens in response to divergent selection for plasma very low density lipoprotein concentration.

1. Plasma lipoprotein metabolism and body composition in lines of chicken selected for high- and low-plasma very low density lipoprotein (VLDL) concentrations were compared to the commercial broiler (meat-type) line from which they were derived. 2. Selection for low-plasma VLDL concentration for 10 generations has reduced the rate of VLDL secretion by at least 50% in males whereas selection for high-VLDL concentration has increased the rate of VLDL secretion over 2-fold. 3. Body fat content was highly correlated with rate of secretion of plasma triglyceride-rich (TGR) lipoproteins (r = 0.88 over the three lines). However, extrapolation of the data suggests that birds secreting no TGR-lipoproteins into the plasma would still have substantial amounts of body fat. 4. Selection for high VLDL has increased the proportion of circulating VLDL-triglyceride taken up by the abdominal fat pad by over 2-fold but there was no difference between high- and low-VLDL lines in the proportion of VLDL-triglyceride taken up by tissues and oxidised to [14C]-carbon dioxide. 5. The results confirm the importance of plasma lipoprotein metabolism in determining body composition in the chicken but suggest there are limits to further reduction in body fat content by manipulation of plasma lipoprotein metabolism.

Adipose Tissue↗

PubMed1983

Uptake of lipoproteins by in situ perfused rat ovaries: identification of binding sites for high density lipoproteins.

We have examined the uptake and distribution of 125I-labeled human high density lipoprotein, apolipoprotein E-free (hHDL3), 125I-rat high density lipoprotein (HDL), and human HDL (hHDL) reconstituted with [3H]cholesteryl linoleate after their in situ vascular perfusion to ovaries of gonadotropin-primed immature rats on days 6-9 post human chorionic gonadotropin (hCG)-injection. Some rats were treated with 4-aminopyrazolopyrimidine to reduce plasma lipoproteins and ovarian cholesteryl ester stores. Perfused ovaries were analyzed biochemically and autoradiographically, and progestin content of the ovarian effluent was quantified. Infusion of ovine luteinizing hormone and hHDL increased ovarian progestin secretion severalfold, indicating that the perfused ovary was functional. After perfusion with HDL reconstituted with [3H]cholesteryl linoleate, radioactive progestin appeared in the effluent; thus, sterol carried by exogenous HDL was converted to steroid. At 37 degrees C, uptake of 125I-hHDL3 was greatest after 15 min of perfusion with label. This was decreased by 80% when the perfusion was carried out at 4 degrees C and by 70-95% when excess unlabeled hHDL, but not human low density lipoprotein (hLDL), was included in the perfusate with 125I-hHDL. Aminopyrazolopyrimidine treatment enhanced 125I-hHDL uptake twofold. After perfusion for 15 min with 125I-hHDL3, radioactivity in the ovary was high for 3-30 min of HDL-free wash, then declined 75% by 30-60 min. With light and electron microscope autoradiography, 125I-hHDL3 was localized to corpora lutea, both along luteal cell surfaces and over their cytoplasm. The plasma membrane grains appeared to be associated with segments that lacked bristle coats. Perfusion with 125I-rat HDL produced a similar pattern of labeling. In ovaries perfused with 125I-BSA, silver grains were concentrated over macrophage-like cells but were sparse over luteal cells. We conclude that the in situ perfused rat ovary takes up 125I-hHDL3 by a temperature-dependent, lipoprotein-specific process, and that this lipoprotein is accumulated by luteal cells.

Adenine↗

PubMed1984

Nutrient intake and its association with high-density lipoprotein and low-density lipoprotein cholesterol in selected US and USSR subpopulations. The US-USSR Steering Committee for Problem Area I: The pathogenesis of atherosclerosis.

Nutrient intake levels and the associations of the nutrients with high-density lipoprotein and low-density lipoprotein cholesterol were studied using cross-sectional data from middle-aged US and USSR men seen at visit 2 of the Lipid Research Clinics Prevalence Study. Differences in nutrient intake in the two countries were small, but statistically significant. The US sample had a higher mean intake of protein, polyunsaturated and monounsaturated fatty acids, and a higher P/S ratio. The USSR sample had higher mean intake of saturated fatty acids, carbohydrate, complex carbohydrate, and sucrose. Correlations between the nutrients and high-density lipoprotein cholesterol were weak and consistently negative for fatty acids, total fat, carbohydrate and its components, and positive for ethanol. The correlations between nutrient intake and low-density lipoprotein cholesterol were even weaker. After adjusting for other factors, nutrient intake had an independent association with high-density lipoprotein cholesterol. Ethanol and carbohydrate showed the strongest association. Nutrient intake also had a modest independent association with low-density lipoprotein cholesterol.

Alcohol Drinking↗