Biomedical subjects

A van Tol

Publications and source records attributed to A van Tol.

At least 55 records · Page 3Linked to original sources

PubMed1998

Plasma phospholipid transfer protein activity is related to insulin resistance: impaired acute lowering by insulin in obese Type II diabetic patients.

Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) have important functions in high density lipoprotein (HDL) metabolism. We determined the association of plasma CETP and PLTP activities (measured with exogenous substrate assays) with insulin resistance, plasma triglycerides (TG) and non-esterified fatty acids (NEFA), and assessed the lipid transfer protein response to insulin during a 6-7 h hyperinsulinaemic euglycaemic clamp in non-obese and obese healthy subjects and patients with Type II (non-insulin-dependent) diabetes mellitus (n = 8 per group). Plasma PLTP activity was higher in obese healthy subjects and obese Type II diabetic patients compared with non-obese healthy subjects (p < 0.05 to 0.01) and was correlated with insulin resistance, plasma TG and NEFA (p = 0.02 to < 0.01). In non-obese healthy subjects, insulin decreased plasma TG and increased the HDL cholesteryl ester (CE)/TG ratio (p < 0.01 compared with saline infusion). Plasma PLTP activity fell by 14% at the end of the clamp (p < 0.01 compared with saline) but CETP activity did not change. The decreases in plasma NEFA, TG and PLTP activity and the rise in HDL CE/TG were smaller in obese Type II diabetic patients than in non-obese healthy subjects (p < 0.01 for all). Baseline HDL CE/TG was negatively correlated with plasma TG (p < 0.001, n = 32) and PLTP activity (p < 0.01) but not with CETP activity. Likewise, the rise in HDL CE/TG during the clamp was related to the fall in plasma TG (p < 0.001) and in PLTP activity (p < 0.02). It is concluded that plasma PLTP, but not CETP, is regulated by insulin in an acute setting. High plasma PLTP activity is associated with insulin resistance in conjunction with altered NEFA and triglyceride metabolism. High plasma TG and PLTP activity have coordinate effects on HDL metabolism.

Adult↗

PubMed1998

Delayed increase in high density lipoprotein-phospholipids after ingestion of a fat load in normolipidemic patients with coronary artery disease.

We studied the effect of a single oral fat load, supplemented with retinyl palmitate (RP), on high density lipoprotein (HDL) lipids in six normolipidemic men with coronary artery disease (CAD) and in six age- and lipid-matched controls. All subjects were selected from a study group which underwent the same protocol 2 years earlier. Post-prandial total plasma lipids, plasma RP levels, and HDL lipids were evaluated at 2-h intervals up till 10 h after the meal. In most subjects the post-prandial response of plasma triglyceride (TG) and plasma RP was identical in the first and second tests. Following the fat load, control subjects showed no change in HDL total cholesterol (TC) or HDL cholesteryl ester (CE) and showed an increase in HDL-TG. CAD subjects however showed a decrease in HDL-TC and HDL-CE and an increase in HDL-TG, similar to the increase in control subjects. In control subjects an increase in HDL phospholipid (PL) was apparent between 0 and 8 h after the fat load. By contrast, in CAD subjects the increase in HDL-PL was only found after as long as 6 h. The magnitude of the post-prandial response of HDL-PL measured during the test was significantly lower in the CAD group. The effects of the fat load on HDL free cholesterol (FC) were similar to the changes in HDL-PL. These data support the hypothesis that PL and FC released during the degradation of chylomicrons as surface remnants are taken up by HDL. This process is clearly delayed in normolipidemic CAD subjects compared with controls. The data suggest that differences in the post-prandial response to an oral fat load in normolipidemic CAD patients and control subjects are not confined to the clearance of TG-rich lipoproteins, but also involve a difference in the uptake of chylomicron surface material by HDL.

Adult↗

PubMed1998

Elevated plasma cholesteryl ester transfer in NIDDM: relationships with apolipoprotein B-containing lipoproteins and phospholipid transfer protein.

Lecithin:cholesteryl acyl transferase (LCAT) and cholesteryl ester transfer protein (CETP) are key factors in the esterification of cholesterol and the subsequent transfer of cholesteryl ester from high density lipoproteins (HDL) towards very low and low density lipoproteins (VLDL + LDL). Phospholipid transfer protein (PLTP), lipoprotein lipase (LPL) and hepatic lipase (HL) are involved in plasma phospholipid and triglyceride metabolism and also affect HDL. Equivocal changes in plasma cholesteryl ester transfer have been reported in non-insulin-dependent diabetes mellitus (NIDDM). In 16 NIDDM men with plasma triglycerides < or = 4.5 mmol/l and cholesterol < or = 8.0 mmol/l. plasma cholesteryl ester transfer (CET), cholesterol esterification rate, LCAT and PLTP activity levels were higher (P < 0.05 to P < 0.02) in conjunction with higher plasma triglycerides (P < 0.01) and lower HDL cholesterol and cholesteryl ester levels (P < 0.05) compared to 16 matched healthy men. Multiple stepwise regression analysis demonstrated that CET was positively related to VLDL + LDL cholesterol (P < 0.001), triglycerides (P = 0.001), PLTP activity (P = 0.007) and CETP activity (P = 0.008, multiple r = 0.94). NIDDM had no effect on CET, independently from these parameters. HDL cholesteryl ester was negatively related to CET (P= 0.017), HL activity (P = 0.033) and NIDDM (P = 0.047) and positively to LCAT activity levels (P = 0.034, multiple r = 0.68). It is concluded that the elevated CET in plasma from NIDDM patients is associated with higher plasma triglycerides and PLTP activity levels. Furthermore, our data suggest that in normo- and moderately dyslipidaemic subjects PLTP and CETP activity levels per se may influence the rate of cholesteryl ester transfer in plasma. Plasma cholesteryl ester transfer appears to be a determinant of HDL cholesteryl ester, but other factors are likely to contribute to lower HDL cholesteryl ester levels in NIDDM.

Adult↗

PubMed1998

Changes in postprandial lipoproteins of low and high density caused by moderate alcohol consumption with dinner.

We measured the effects of consumption of moderate amounts of beer, wine or spirits with evening dinner on plasma LDL and HDL levels as well as composition in 11 healthy middle-aged men. Forty grams of alcohol were consumed daily with dinner for a period of 3 weeks. Mineral water was used as a negative control. Dinner was served at 6 pm and blood samples were obtained at 1 h before and 3, 5, 9, and 13 h after the start of the meal. No differences were detected between the effects of the different alcohol-containing beverages. Plasma levels of triglycerides (TG), measured 1 h before dinner were very variable and higher than fasting values (means of 2.2 and 1.5 mM, respectively). Daily consumption of 40 g of alcohol with dinner resulted in increased postprandial plasma TG levels and decreased low density lipoprotein (LDL) cholesterol concentrations. These effects were transient and observed at 11 pm (TG) and 9 pm and 11 pm (LDL). In contrast, high density lipoproteins (HDL) were raised by alcohol intake at all time points analysed. HDL composition was changed by alcohol consumption, resulting in a raised HDL-cholesterol/apo A-I ratio at 5 pm and 9 pm. The observed alcohol-dependent effects on plasma HDL and LDL during the postprandial phase are considered anti-atherogenic and may contribute to the observed protection against coronary heart disease by moderate alcohol consumption.

Adult↗

PubMed1998

A linoleic acid enriched diet increases serum cholesterol esterification by lecithin:cholesterol acyltransferase in meal-fed rats.

Dietary fats are known to influence the fatty acid profile of plasma lipids, including phospholipids which are substrates of lecithin:cholesterol acyltransferase (LCAT; EC 2.3.1.43), an important enzyme in lipoprotein metabolism. We tested whether the dietary fatty acid profile has an effect on LCAT activity in an animal model. Rats were conditioned to eat two meals per day, which were enriched in either palmitic, oleic or linoleic acids, for 10 weeks. Serum was isolated from blood samples taken prior to the meal. The LCAT activity was determined in two ways: (1) by measuring serum cholesterol esterification rates, which are an estimate of LCAT action on endogenous lipoproteins, and (2) by measuring serum LCAT activity levels with excess exogenous substrates, an estimate of LCAT mass. Animals receiving the linoleic acid diet had lower serum concentrations of unesterified cholesterol and triglycerides, if compared with animals fed oleic acid or palmitic acid diets (p < 0.05). Serum LCAT activity levels (measured with excess exogenous substrates) were not different, but both the absolute and fractional rates of cholesterol esterification were highest on the linoleic acid rich diet (p < 0.01), showing that LCAT action on endogenous lipoproteins is improved. No differences were found in serum apolipoprotein B and A-IV concentrations between the dietary groups. Apolipoprotein A-I levels were lowest in the palmitic acid group (oleic and linoleic > palmitic; p < 0.05), and apolipoprotein E levels were highest in the palmitic acid group (palmitic > oleic and linoleic; p < 0.05). It is concluded that a linoleic acid rich diet may cause increased metabolism of serum cholesterol by LCAT in rats. This effect is not due to elevated serum concentrations of LCAT or of its apolipoprotein activators, but most likely to changes in the chemical composition of endogenous lipoprotein substrates. It remains to be established whether the serum cholesterol esterification rates measured in vitro are related to in vivo rates of reverse cholesterol transport.

Animal Feed↗

PubMed1998

A mutation in the lipoprotein lipase gene associated with hyperlipoproteinemia type I in mink: studies on lipid and lipase levels in heterozygotes.

Severe hypertriglyceridemia was previously observed in mink. Affected animals had no detectable lipoprotein lipase activity, but normal amounts of lipoprotein lipase protein in post-heparin plasma. We have now cloned cDNA for lipoprotein lipase from normal mink and identified a single point mutation in the affected animals which most likely explains the deficiency of active lipase. The mutation is located in exon 6 and results in a Pro214Leu substitution. In heterozygote mink the levels of lipoprotein lipase activity and mass in post-heparin plasma were lower than in normal mink, but could not be used to identify carriers of the mutation. In some tissues (heart, muscle, kidney and lung), lipoprotein lipase activity was decreased to about 50%. In adipose tissue there seemed to be a mechanism to compensate for the mutation, resulting in increased mass and approximately the same activity of lipoprotein lipase as in animals not carrying the mutation. Mink had high lipoprotein lipase activity and mass in kidneys, although the levels of mRNA in kidney were many fold lower than in adipose tissue. Mink had very low levels of cholesteryl ester transfer protein activity in plasma. This may contribute to the high levels of HDL in this animal species.

Adipose Tissue↗

PubMed1997

The cholesterol-raising diterpenes from coffee beans increase serum lipid transfer protein activity levels in humans.

Cafestol and kahweol-diterpenes present in unfiltered coffee-strongly raise serum VLDL and LDL cholesterol and slightly reduce HDL cholesterol in humans. The mechanism of action is unknown. We determined whether the coffee diterpenes may affect lipoprotein metabolism via effects on lipid transfer proteins and lecithin:cholesterol acyltransferase in a randomized, double-blind cross-over study with 10 healthy male volunteers. Either cafestol (61-64 mg/day) or a mixture of cafestol (60 mg/day) and kahweol (48-54 mg/day) was given for 28 days. Serum activity levels of cholesterylester transfer protein, phospholipid transfer protein and lecithin:cholesterol acyltransferase were measured using exogenous substrate assays. Relative to baseline values, cafestol raised the mean (+/- S.D.) activity of cholesterylester transfer protein by 18 +/- 12% and of phospholipid transfer protein by 21 +/- 14% (both P < 0.001). Relative to cafestol alone, kahweol had no significant additional effects Lecithin:cholesterol acyltransferase activity was reduced by 11 +/- 12% by cafestol plus kahweol (P = 0.02). It is concluded that the effects of coffee diterpenes on plasma lipoproteins may be connected with changes in serum activity levels of lipid transfer proteins.

Adult↗

PubMed1997

Higher high density lipoprotein cholesterol associated with moderate alcohol consumption is not related to altered plasma lecithin:cholesterol acyltransferase and lipid transfer protein activity levels.

Lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are important factors involved in HDL metabolism. Altered plasma activity levels of these factors could play a role in the increase in high density lipoprotein (HDL) cholesterol associated with moderate alcohol consumption. We measured plasma LCAT, CETP and PLTP activities with exogenous substrate assays, as well as lipoproteins and HDL lipids in 6 alcohol-abstaining men, 18 matched men who used < or = 1 and 18 men who used > or = 1 alcohol-containing drinks per day. Plasma cholesterol and triglycerides were similar in the three groups. HDL total cholesterol, HDL cholesteryl ester, HDL free cholesterol and HDL triglycerides were higher in the alcohol drinkers compared to the abstainers (all P < 0.05). No differences in plasma LCAT, CETP and PLTP activity levels were observed between the three groups. Analysis of covariance also demonstrated that the use of alcohol was associated with higher HDL cholesterol (P < 0.04), whereas plasma LCAT, CETP and PLTP activity levels were not related to alcohol consumption. Furthermore, HDL cholesteryl ester was positively associated with LCAT activity (P < 0.001), PLTP activity (P < 0.01) and alcohol intake (P < 0.04) and negatively with plasma triglycerides (P < 0.001) and CETP activity (P < 0.03); indicating that alcohol influenced HDL cholesteryl ester independently from these biochemical parameters. The higher HDL cholesterol associated with moderate alcohol consumption is, therefore, unlikely to be caused by and effect on plasma LCAT, CETP or PLTP activity levels.

Adolescent↗

PubMed1997

Hyperlipidemia is secondary to proteinuria and is completely normalized by angiotensin-converting enzyme inhibition in hypertensive fawn-hooded rats.

Two substrains of the fawn-hooded (FH) rat have been developed, one of which develops progressive hypertension and proteinuria, the FHH, and one which shows little increase in blood pressure and no renal damage, the FHL. Other hypertensive rodent models show primary metabolic disturbances before the development of renal damage, notably hypertriglyceridemia, which may also contribute to progression of renal disease. In this study we evaluated whether hyperlipidemia is a primary disturbance in FHH, or only occurs secondary to proteinuria. Lipid levels were determined before and after development of proteinuria, and compared to those found in age-matched FHL. We also determined whether reducing proteinuria with lisinopril would normalize lipid levels in aging FHH. At 4 weeks of age, proteinuria was very low (2-3 mg/day) in both FHH and FHL. While proteinuria increased steadily in aging FHH, reaching 350 +/- 62 mg/day at 40 weeks, much less increase was observed in FHL over the same period (32 +/- 5 mg/day at 40 weeks). Blood pressure was markedly higher in adult FHH than in FHL (158 +/- 2 vs. 129 +/- 2 mm Hg, p < 0.01). In 4-week-old FHL and FHH, plasma cholesterol levels were similar. Subsequently, cholesterol increased in FHH, reaching 3.4 +/- 0.9 mmol/l at 40 weeks, whereas cholesterol was barely affected by aging in FHL (2.1 +/- 0.2 mmol/l at 40 weeks). At 4 weeks, triglyceride levels were lowest in FHH. Subsequently, triglycerides increased in FHH, reaching 3.5 +/- 1.5 mmol/l at 40 weeks, as compared to 1.3 +/- 0.2 mmol/l in FHL. Besides a transient increase in triglyerides in lisinopril-treated FHH at 11 weeks, increments in blood pressure, proteinuria, cholesterol, triglycerides and apolipoproteins A-I, B and E aging FHH were effectively prevented by lisinopril. These data strongly suggest that there is no primary difference in lipid metabolism between FHH and FHL and that changes in plasma lipids in FHH as compared to FHL are all secondary to proteinuria.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1997

Estrogen replacement during hypoalbuminemia may enhance atherosclerotic risk.

Estrogen replacement therapy is considered antiatherosclerotic because it reduces LDL cholesterol and fibrinogen and increases HDL cholesterol concentrations. However, exogenous estrogen is also known to increase hepatic triglyceride production. Hyperlipidemia in the nephrotic syndrome is probably due to increased lipoprotein secretion into plasma and decreased clearance of lipoprotein cholesterol and triglycerides. Previously, lipid-lowering effects of ovariectomy in analbuminemic rats were observed, suggesting that in the presence of hypoalbuminemia, estrogen replacement may have adverse effects on the lipid profile. To test this hypothesis, ovariectomized control rats and rats with Adriamycin-induced nephrotic syndrome were treated with estradiol. In ovariectomized controls, estradiol reduced plasma LDL cholesterol, apolipoprotein B, and fibrinogen and increased apolipoprotein A-I and triglycerides. Nephrotic rats were characterized by a marked decrease in plasma colloid osmotic pressure, hyperfibrinogenemia, hyperlipidemia, and stimulated hepatic fatty acid synthesis. The beneficial effects of estradiol on LDL cholesterol, apolipoprotein B, and fibrinogen found in ovariectomized controls were not present in estradiol-treated nephrotic rats. This suggests that in hypoalbuminemia, downregulation of the LDL receptor overrides putative estradiol-induced increases in LDL receptor activity. Moreover, estrogen replacement in the nephrotic syndrome doubled fatty acid synthesis and triglyceride secretion, and markedly exacerbated hypertriglyceridemia, suggesting saturation of triglyceride clearance. Thus, severe hypoalbuminemia in rats induces an atherosclerotic metabolic response that is aggravated by estrogen replacement. These findings suggest that estrogen replacement in hypoalbuminemic subjects could be contra-indicated.

Animals↗

PubMed1997

Cholesteryl ester transfer protein gene polymorphism is a determinant of HDL cholesterol and of the lipoprotein response to a lipid-lowering diet in type 1 diabetes.

The TaqIB cholesteryl ester transfer protein (CETP) gene polymorphism (B1B2) is a determinant of HDL cholesterol in nondiabetic populations. Remarkably, this gene effect appears to be modified by environmental factors. We evaluated the effect of this polymorphism on HDL cholesterol levels and on the lipoprotein response to a linoleic acid-enriched, low-cholesterol diet in patients with type 1 diabetes. In 44 consecutive type 1 diabetic patients (35 men), CETP polymorphism, apolipoprotein (apo) E genotype, serum lipoproteins, serum CETP activity (measured with an exogenous substrate assay, n = 30), clinical variables, and a diet history were documented. The 1-year response to diet was assessed in 14 type 1 diabetic patients, including 6 B1B1 and 6 B1B2 individuals. HDL cholesterol was higher in 10 B2B2 than in 14 B1B1 homozygotes (1.63 +/- 0.38 vs. 1.24 +/- 0.23 mmol/l, P < 0.01). HDL cholesterol, adjusted for triglycerides and smoking, was 0.19 mmol/l higher for each B2 allele present. CETP activity levels were not significantly different between CETP genotypes. Multiple regression analysis showed that VLDL + LDL cholesterol was associated with dietary polyunsaturated:saturated fatty acids ratio (P < 0.02) and total fat intake (P < 0.05) in the B1B1 homozygotes only and tended to be related to the presence of the apo E4 allele (P < 0.10). In response to diet, VLDL + LDL cholesterol fell (P < 0.05) and HDL cholesterol remained unchanged in 6 B1B1 homozygotes. In contrast, VLDL + LDL cholesterol was unaltered and HDL cholesterol decreased (P < 0.05) in 6 B1B2 heterozygotes (P < 0.05 for difference in change in VLDL + LDL/HDL cholesterol ratio). This difference in response was unrelated to the apo E genotype. Thus, the TaqIB CETP gene polymorphism is a strong determinant of HDL cholesterol in type 1 diabetes. This gene effect is unlikely to be explained by a major influence on the serum level of CETP activity, as an indirect measure of CETP mass. Our preliminary data suggest that this polymorphism may be a marker of the lipoprotein response to dietary intervention.

Adult↗

PubMed1996

Ovariectomy decreases plasma triglyceride levels and both prevents and alleviates glomerular disease in uninephrectomized female analbuminemic rats.

Female Nagase analbuminemic rats (NAR) are profoundly hypertriglyceridemic and develop proteinuria and glomerulosclerosis when aging and after uninephrectomy (UNX). Ovariectomy (OVX) markedly decreases plasma triglyceride levels in this species. This study evaluated whether decreasing triglyceride levels by OVX could prevent renal disease or alleviate its progression in UNX female NAR. Female NAR underwent OVX at 0, 12, 24, or 36 wk after UNX. In the absence of OVX, the animals developed progressive proteinuria from 18 wk after UNX and showed extensive glomerular sclerosis, lipid deposition, and hypertrophy at euthanasia (49 wk after UNX). These changes were prevented by OVX carried out at 0 or 12 wk, and attenuated by OVX at 24 wk after UNX. If performed at 36 wk after UNX, OVX had no effect on glomerulosclerosis, although it reduced proteinuria. In 95% (20 of 21) of the rats with proteinuria over 10 mg/day, proteinuria decreased in the first 6 wk after OVX. The percentage decrease in proteinuria correlated inversely with the glomerulosclerosis score at euthanasia (r = -0.58, P < 0.01). OVX had no effect on hyperfiltration and hyperperfusion in the UNX rats. OVX consistently reduced plasma triglyceride levels in rats both with and without proteinuria, and it also reduced plasma cholesterol, but only in conjunction with reduction in proteinuria. It was concluded that OVX in UNX female NAR prevents glomerulosclerosis if performed before proteinuria and attenuates further development of established renal disease if performed in a timely manner. This study's data suggest that in UNX female NAR, the lowering of plasma triglyceride levels plays a central role in the renoprotective action of OVX.

Aging↗

PubMed1996

Effect of plasma oncotic pressure on apolipoprotein levels in rats with Heymann nephritis.

The nephrotic syndrome is characterized by reduced plasma albumin and colloid osmotic pressure (pi). Infusion of dextran or albumin reduces lipid levels suggesting that reduced plasma pi plays a role in causing hyperlipidemia in the nephrotic syndrome. To determine whether apolipoprotein (Apo) levels were affected by pi, passive Heymann nephritis (HN) was created in 20 rats. Hyperoncotic (25%) human albumin or ficoll was infused continuously into each of 5 HN rats adjusted to maintain a plasma pi above 20 mm Hg. Either saline or a mixture of amino acids calculated to approximate those released from catabolized human albumin were infused into 5 HN as controls. Urinary rat albumin loss was not different between the 4 groups of HN. Plasma apo A-I, B and E were all increased significantly in saline and amino acid infused HN, but apo A-IV was decreased. Infusion of either albumin or ficoll normalized apo A-I, and apo E levels in HN even though proteinuria continued unabated. In contrast, apo B remained significantly elevated in HN infused with albumin, but was reduced to normal by ficoll. Fifteen non-nephrotic control animals were studied in 3 groups of 5 animals each; one receiving human albumin, one ficoll, both adjusted to increase plasma pi to supranormal levels, and a 3rd group received saline. In contrast to HN, plasma apo A-I, E, and B levels were unaffected by albumin or ficoll infusion in control animals. Ficoll caused a significant reduction in apo A-IV in both HN and control animals to subnormal levels, but albumin infusion was without effect. Reduced plasma pi, but not reduced plasma albumin is necessary for increased apo A-I, and E levels in the nephrotic syndrome. When plasma pi is normal extensive proteinuria does not increase plasma apo A-I or E levels. Factors other than an albumin concentration or pi, such as persistent urinary protein loss, play a role in establishing increased apo B containing lipoproteins in the nephrotic syndrome. Ficoll may cause changes in plasma lipoprotein levels by means other than its ability to increase plasma pi.

Animals↗

PubMed1995

Dietary trans fatty acids increase serum cholesterylester transfer protein activity in man.

The average diet may provide some 8-10 g/day of unsaturated fatty acids with a trans double bond. Previous studies showed that dietary trans fatty acids may simultaneously raise low-density lipoprotein (LDL) cholesterol and reduce high-density lipoprotein (HDL) cholesterol. Human plasma contains a protein (CETP) which transfers cholesterylesters from HDL to lipoproteins of lower density. We hypothesized that CETP could play a role in the effect of trans fatty acids on lipoproteins and measured the activity levels of CETP in serum samples from a 9-week study in which 55 volunteers were fed three controlled diets with different fatty acid profiles. Mean activity was 114 (% of reference serum) after consumption of a high trans fatty acid diet, as opposed to 96 after linoleic acid and 97 after stearic acid (P < 0.02). We conclude that the increased activity of CETP may contribute to the rise in LDL cholesterol and the fall in HDL cholesterol seen on diets with high contents of trans fatty acids.

Analysis of Variance↗

PubMed1995

Dialysis of isolated low density lipoprotein induces a loss of lipophilic antioxidants and increases the susceptibility to oxidation in vitro.

We determined the effects of different dialysis conditions on the antioxidant content, duration of the lag phase and oxidation rate of LDL. Dialysis for 22 h resulted in a 56%--66% reduction in the concentrations of beta-carotene, lycopene and alpha-tocopherol. The lag phase of copper-induced oxidation of freshly isolated LDL was considerably longer than that of LDL dialysed for 22 or 44 h. Our data show that dialysis may result in LDL preparations with antioxidant compositions that are not truly representative of freshly isolated lipoproteins.

Adult↗

PubMed1995

Ovariectomy decreases plasma triglyceride levels in analbuminaemic rats by lowering hepatic triglyceride secretion.

In mutant analbuminaemic rats (NAR), females demonstrate a more marked hypertriglyceridaemia than males. Ovariectomy decreases triglyceride levels in female NAR. We measured triglyceride secretion rates in vivo as well as the activity of acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS) in hepatic cytosol obtained from female control Sprague-Dawley (SD) rats and NAR with or without ovariectomy. NAR were severely hyperlipidaemic, and triglyceride, cholesterol, apolipoprotein A-I and plasma protein concentrations levels were decreased (all P < 0.01) by ovariectomy. Only triglyceride levels were decreased by ovariectomy in the SD rats (P < 0.05). Oestradiol treatment in ovariectomized NAR restored plasma protein and triglyceride concentrations to levels similar to those observed in intact female NAR and caused a marked increase in plasma cholesterol. Ovariectomy in NAR reduced lipoprotein triglycerides and cholesterol in VLDL, IDL and LDL1, but had little effect on the triglyceride-cholesterol ratio of these particles. Both ACC and FAS activities were markedly increased in NAR vs. SD rats (P < 0.01). This increase was partially corrected by ovariectomy. There was no significant effect of ovariectomy on ACC or FAS activity in the SD rats. Triglyceride secretion rates were significantly increased in NAR vs. SD rats (135 +/- 10 vs. 103 +/- 12 nmol/min per 100 g body weight; P < 0.05). Ovariectomy markedly decreased triglyceride secretion rate in NAR to 69 +/- 6 (P < 0.01), but not in SD rats (92 +/- 8 nmol/min per 100 g body weight, NS). Oestradiol treatment in ovariectomized SD rats restored triglyceride levels but had no significant effect on triglyceride secretion rate (106 +/- 23 nmol/min per 100 g).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetyl-CoA Carboxylase↗

PubMed1995

Effect of oncotic pressure on apolipoprotein A-I metabolism in the rat.

The nephrotic syndrome is characterized by reduced plasma albumin and colloid osmotic pressure (pi), urinary protein loss and hyperlipidemia. High-density lipoprotein (HDL) and the level of apo A-I, the principal apolipoprotein in HDL, is increased in nephrotic rats and rats with hereditary analbuminemia (NAR)--animals with virtually no albumin in plasma and reduced plasma pi, but without proteinuria, suggesting that urinary protein loss is not responsible for increased plasma apo A-I levels. We conducted these studies to determine the mechanism responsible for increased plasma apo A-I levels in the nephrotic syndrome and NAR and to determine whether reduced plasma pi or albumin was responsible for increased apo A-I. We first measured the clearance of 125I apo A-I HDL in NAR and rats with passive Heymann nephritis (HN) compared with normal Sprague Dawley (SD) control. Both the clearance of apo A-I and fractional apo A-I turnover rate (FTR) were significantly reduced both in HN (7.40 +/- 2.18% plasma pool/hr) and NAR (5.63 +/- 1.12) compared with SD (9.87 +/- 0.75). Total apo A-I turnover rate, which in steady state equals apo A-I synthesis rate, was also significantly increased in both HN (487 +/- 127 micrograms/100 g body weight/hr) and NAR (253 +/- 16), compared with SD (216 +/- 19). Thus decreased apo A-I catabolism and increased synthesis both contributed to increased apo A-I levels in HN and NAR. We then infused either f3p4roncotic human albumin or ficoll into two additional groups of HN for days in quantities sufficient to maintain plasma pi within the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Proteinuria, lipoproteins and renal apolipoprotein deposits in uninephrectomized female analbuminemic rats.

To elucidate the pathogenetic role of hyperlipidemia per se in the development of glomerulosclerosis, severely hyperlipidemic female analbuminemic rats (NAR) and mildly hyperlipidemic male NAR were studied for a period of 37 weeks after uninephrectomy (UNX). Plasma cholesterol increased from 6.3 +/- 0.4 (week 4) to 11.9 +/- 0.6 mmol/liter (week 37) in the female NAR, and from 4.3 +/- 0.1 to 6.4 +/- 0.5 mmol/liter in the male NAR in the same period. Plasma protein concentration was also consistently higher in female NAR (60 +/- 1 g/liter) as compared to male NAR (52 +/- 1 g/liter). Plasma viscosity was higher in female NAR than in male NAR, but there were no differences in blood viscosity. Proteinuria increased progressively in the UNX female NAR from 25 weeks after surgery, reaching a final value of 141 +/- 37 mg/day. No proteinuria occurred in the UNX male NAR (final value 15 +/- 2 mg/day). Glomerular capillary pressure, measured prior to the onset of proteinuria, was not significantly different in UNX female NAR and UNX male NAR. At the end of the study glomerulosclerosis and lipid deposition was only found in the UNX female NAR. Throughout the study hyperfiltration and hyperperfusion, relative to the one-kidney clearances of the sham-operated (2K) animals, were not different in UNX male and female NAR. No differences were observed in blood pressure. Hypertrophy, evaluated by glomerular diameters, was less pronounced in UNX female NAR (174 +/- 3 microns) than in UNX male NAR (190 +/- 7 microns). Glomerular diameters in 2K female and male NAR were similar (respectively 158 +/- 2 and 157 +/- 4 microns). Plasma apo B levels were similar (2K female NAR: 204 +/- 8 U; 2K male NAR 204 +/- 13 U), but cholesterol and triglyceride content of apo B-containing lipoproteins, namely VLDL, IDL and LDL, was increased twofold in the female NAR as compared to the male NAR, implying a larger particle size in the female NAR. Deposition of apo B and apo E was observed in the glomerular mesangium of UNX female NAR, particularly in sclerotic lesions. Glomerular apo A-I deposits were localized primarily in visceral epithelial cells and were not associated with sclerotic lesions. The development of proteinuria and glomerulosclerosis after UNX in female NAR but not in male NAR may depend upon differences in plasma lipoprotein composition, but is apparently not related to differences in whole kidney hyperfiltration and hyperperfusion, glomerular capillary pressure, or blood viscosity.

Animals↗