Serum Very Low Density Lipoprotein Cholesterol Research Articles

Rumen-protected choline reduces hepatic lipidosis by increasing hepatic triacylglycerol-rich lipoprotein secretion in dairy cows

Objectives were to determine the effects of supplementing rumen-protected choline (RPC) on hepatic composition and secretion of triacylglycerol-rich lipoprotein when cows were subjected to feed restriction to develop fatty liver. It was hypothesized that RPC reduces hepatic triacylglycerol by enhancing secretion of hepatic lipoprotein. Pregnant, nonlactating parous Holstein cows (n = 33) at mean (± standard deviation) 234 ± 2.2 d of gestation were blocked by body condition (3.79 ± 0.49) and assigned to receive 0 g/d (CON), 25.8 g/d choline ion from a RPC product containing 28.8% choline chloride (CC; treatment L25.8), or 25.8 g/d of choline ion from a RPC product containing 60.0% CC (H25.8). Cows were fed for ad libitum intake for the first 5 d and restricted to 41% of the net energy for lactation required for maintenance and pregnancy from d 6 to 13. Intake of metabolizable methionine was maintained at 18 g/d during feed restriction by supplying rumen-protected methionine. Hepatic tissue was sampled on d 6 and 13 and analyzed for triacylglycerol and glycogen, and mRNA expression of hepatic tissue was investigated. On d 14, cows were not fed and received a 10% solution of tyloxapol intravenously at 120 mg/kg of body weight to block hydrolysis of triacylglycerols in very low density lipoprotein (VLDL). Blood was sampled sequentially for 720 min and analyzed for concentration of triacylglycerol and total cholesterol. Lymph was sampled 6 h after tyloxapol infusion, and analyzed for concentrations of fatty acids, β-hydroxybutyrate, glucose, triacylglycerol, and total cholesterol. A sample of serum collected at 720 min after tyloxapol was assayed for the metabolome composition. The area under the curve (AUC) of serum triacylglycerol, VLDL cholesterol, and total cholesterol were calculated. Orthogonal contrasts evaluated the effect of supplementing RPC (CON vs. [1/2 L25.8 + 1/2 H25.8]) and source of RPC (L25.8 vs. H25.8). Least squares means and standard errors of the means are presented in sequence as CON, L25.8, H25.8. During feed restriction, supplementation of RPC reduced hepatic triacylglycerol (9.0 vs. 4.1 vs. 4.5 ± 0.6%) and increased glycogen contents (1.9 vs. 3.5 vs. 4.1 ± 0.2%). Similarly, supplementation of RPC increased the expression of transcripts involved in the synthesis and assembly of lipoproteins (MTTP), cellular autophagy (ATG3), and inflammation (TNFA), and reduced the expression of transcripts associated with mitochondrial oxidation of fatty acids (HADHA, MLYCD) and stabilization of lipid droplets (PLIN2). After infusion of tyloxapol, RPC increased the AUC for serum triacylglycerol (21,741 vs. 32,323 vs. 28,699 ± 3,706 mg/dL × min) and VLDL cholesterol (4,348 vs. 6,465 vs. 5,740 ± 741 mg/dL × min) but tended to reduce the concentrations of triacylglycerol in lymph (16.7 vs. 13.8 vs. 11.9 ± 1.9 mg/dL). Feeding RPC tended to increase the concentrations of 89 metabolites in serum, after adjusting for false discovery, including 3 acylcarnitines, 1 AA-related metabolite, 11 bile acids, 1 ceramide, 6 diacylglycerols, 2 dihydroceramides, 1 glycerophospholipid, and 64 triacylglycerols compared with CON. Feeding 25.8 g/d of choline ion as RPC mediated increased hepatic triacylglycerol secretion to promote lipotropic effects that reduced hepatic lipidosis in dairy cows.

Glycative Stress, Glycated Hemoglobin, and Atherogenic Dyslipidemia in Patients with Hyperlipidemia.

(1) Background: Diabetes mellitus (DM) is a significant health problem and is associated with dyslipidemia; however, the association between glycative stress, in terms of glycated hemoglobin (HbA1c), and atherogenic dyslipidemia in hyperlipidemic patients with and without DM has rarely been reported. (2) Methods: We prospectively recruited 949 hyperlipidemic patients from the Lipid Clinic of the National Taiwan University Hospital. HbA1c and fasting serum lipids, including total cholesterol (TC), high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), small dense LDL-C (sdLDL-C), very low-density lipoprotein cholesterol (VLDL-C), triglycerides, and advanced glycation end-products (AGEs), were measured. After fasting for 10-14 h, all subjects except those with DM underwent a standard oral glucose tolerance test (OGTT) with 75 g of glucose loading. All subjects were asked to discontinue the use of lipid-lowering agents for 8 weeks before recruitment. (3) Results: Patients with DM had a higher prevalence of hypertension and higher levels of triglyceride, TC/HDL-C ratio, AGEs, VLDL-C, and sdLDL-C. Among patients with higher HbA1c, the serum VLDL-C, AGEs, and TC/HDL-C ratio were significantly higher than those with lower HbA1c. After adjustment for covariates, multiple logistic regression analyses revealed different groups of dysglycemia with higher HbA1c had a higher odds ratio for TC/HDL-C ≥ 5, sdLDL-C ≥ 75th percentile, VLDL-C ≥ 75th percentile and AGEs ≥ 75th percentile. (4) Conclusions: A higher HbA1c was associated with a significant increase in the risk of atherogenic dyslipidemia and AGEs levels in patients with hyperlipidemia. The findings can be very promising in clinical application.

Acute Cholesterol-Lowering Effect of Exendin-4 in Ldlr-/- and C57BL/6J Mice.

We previously reported that glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduced serum low-density lipoprotein cholesterol (LDL-C) levels in patients with type 2 diabetes mellitus receiving statins, which increased LDL receptor (LDLR) expression. Nevertheless, it remains unclear how much LDLR expression contributes to the LDL-C-lowering effect of GLP-1RAs. We examined the effect of a GLP-1RA, namely, exendin-4, on serum LDL-C levels and its mechanism in Ldlr-/- and C57BL/6J mice. Ten-week-old Ldlr-/- and C57BL/6J mice received exendin-4 or saline for 5 days, and serum lipid profiles and hepatic lipid levels were examined. Cholesterol metabolism-related gene expression and protein levels in the liver and ileum and the fecal bile acid (BA) composition were also examined. Exendin-4 treatment significantly decreased serum very-low-density lipoprotein cholesterol (VLDL-C) and LDL-C levels and mature hepatic SREBP2 levels and increased hepatic Insig1/2 mRNA expression in both mouse strains. In Ldlr-/- mice, exendin-4 treatment also significantly decreased hepatic cholesterol levels and fecal BA excretion, decreased hepatic Cyp7a1 mRNA expression, and increased small intestinal Fgf15 mRNA expression. In C57BL/6J mice, exendin-4 treatment significantly decreased small intestinal NPC1L1 levels. Our findings demonstrate that exendin-4 treatment decreased serum VLDL-C and LDL-C levels in a manner that was independent of LDLR. Exendin-4 treatment might decrease serum cholesterol levels by lowering hepatic SREBP2 levels and cholesterol absorption in Ldlr-/- and C57BL/6J mice. Exendin-4 treatment might decrease cholesterol absorption by different mechanisms in Ldlr-/- and C57BL/6J mice.

Dose-response relationship between dietary choline and serum lipid profile, energy expenditure, and respiratory quotient in overweight adult cats fed at maintenance energy requirements.

Choline is an essential nutrient linked to hepatic lipid metabolism in many animal species, including cats. The current study investigated the serum lipid profiles, serum liver enzymes, respiratory quotients, and energy expenditures of overweight cats fed maintenance diets, in response to graded doses of supplemental dietary choline. Overweight (body condition score [BCS]: ≥6/9) adult male neutered cats (n = 14) were supplemented with five choline chloride doses for 3-wk periods, in a 5 × 5 Latin square design. Doses were based on individual body weight (BW) and the daily recommended allowance (RA) for choline (63 mg/kg BW0.67) according to the National Research Council. Doses were control (no additional choline: 1.2 × RA, 77 mg/kg BW0.67), 2 × RA (126 mg/kg BW0.67), 4 × RA (252 mg/kg BW0.67), 6 × RA (378 mg/kg BW0.67), and 8 × RA (504 mg/kg BW0.67). Choline was top-dressed over the commercial extruded cat food (3,620 mg choline/kg diet), fed once a day at maintenance energy requirements (130 kcal/kgBW0.4). Body weight and BCS were assessed weekly. Fasted blood samples were taken and indirect calorimetry was performed at the end of each 3-wk period. Serum was analyzed for cholesterol, high-density lipoprotein cholesterol (HDL-C), triglycerides, non-esterified fatty acids, glucose, creatinine, blood urea nitrogen (BUN), alkaline phosphatase (ALP), and alanine aminotransferase. Very low-density lipoprotein cholesterol (VLDL) and low-density lipoprotein cholesterol were calculated. Data were analyzed via SAS using proc GLIMMIX, with group and period as the random effects, and treatment as the fixed effect. Statistical significance was considered at P < 0.05. Body weight and BCS did not change (P > 0.05). Serum cholesterol, HDL-C, triglycerides, and VLDL increased with 6 × RA (P < 0.05). Serum ALP decreased with 8 × RA (P = 0.004). Choline at 4 × and 6 × RA decreased serum BUN (P = 0.006). Fed or fasted respiratory quotient and energy expenditure did not differ among dietary choline doses (P > 0.05). These results suggest that dietary choline supplementation at 6 × RA may increase hepatic fat mobilization through increased lipoprotein transport and beneficially support hepatic health in overweight cats. Future studies that combine these results with existing knowledge of feline weight loss and hepatic lipidosis are warranted.

Effect of vegetable oils supplementation on serum biochemical profile of lactating surti goats and their kids

A study was conducted to observe the effect of soybean and rice bran oil supplementation on serum biochemical profile of Surti goats and their nursing kids during December 2016 to April 2017. Multiparous lactating Surti does (n=24) were distributed into four groups in completely randomized design for entire lactation period of 150 days. The goats of control (CON) group were offered a basal diet consisting of concentrate, chaffed green and dry fodder. The goats of treatment groups viz., SBO (soybean oil @ 3% of DMI (dry matter intake), RBO (rice bran oil @ 3% of DMI) and SRBO (soybean oil @ 1.5% + rice bran oil @ 1.5% of DMI) were supplemented with different vegetable oils along with basal diet. Kids from does of respective treatment groups were also assigned the same group for evaluating the growth performance. Blood sample were collected on 0, 30, 60, 90,120 and 150 days from lactating does and on 45 and 50 days of age in kids. Serum glucose, total protein, triglycerides, LDL (low-density lipoprotein) and VLDL (very low-density lipoprotein) cholesterol and urea nitrogen were neither affected by diet nor time in does of different treatment groups and their respective nursing kids. However, total and HDL (High-density lipoprotein) cholesterol were significantly (P<0.05) improved in lactating does supplemented with oils than the control. Further, maternal dietary lipid sources modified and improved circulatory lipid profile in suckling kids. However, average daily gain in nursing kids remained non-significant among the treatment groups. It was concluded that dietary supplementation of vegetable oil either alone or in combination can be effectively used to improvecirculatory lipidprofile of does andtheirnursing kids.

Elevated Levels of Very Low-density Lipoprotein Cholesterol Independently Associated with In-stent Restenosis in Diabetic Patients after Drug-eluting Stent Implantation.

Background:High rate of in-stent restenosis (ISR) remained an unsolved clinical problem in clinical practice, especially among patients with diabetes mellitus (DM). Diabetic patients often had hypertriglyceridemia with elevated levels of very low-density lipoprotein cholesterol (VLDL-C). Increasing evidence suggested that VLDL-C was known as a significant risk factor for atherosclerosis and had been recommended as a treatment target by current dyslipidemia guidelines. However, the role of VLDL-C in the occurrence and development of ISR in coronary artery disease (CAD) patients with DM had not been studied. The aim of this study was to evaluate the association between the elevated levels of VLDL-C and the risk of ISR in CAD patients with DM.Methods:A total of 1390 diabetic patients, who underwent coronary drug-eluting stent (DES) implantation at Beijing Anzhen Hospital and followed up by angiography within 6–24 months, were consecutively enrolled. Patients’ demographic and clinical characteristics, including age, gender, CAD risk factors, family history, life style, medical history, and coronary angiographic information, were collected carefully at baseline percutaneous coronary intervention and follow-up angiography. Multivariate Cox's proportional hazards regression modeling using the step-wise method (entry, 0.05; removal, 0.05) was used to determine the independent risk associated with ISR in diabetic patients.Results:Finally, 1206 of patients were included in this study. ISR occurred in 132/1206 diabetic patients (10.9%) by follow-up angiography. Patients with ISR had elevated median serum VLDL-C levels compared with those without ISR (0.65 mmol/L vs. 0.52 mmol/L, P = 0.030). The multivariate regression analysis showed that VLDL-C was significantly associated with the risk of ISR in diabetic CAD patients (hazard ratio [HR] = 1.15, 95% confidence interval [CI]: 1.03–1.29, P = 0.017). The HR for the risk of ISR associated with VLDL-C level ≥0.52 mmol/L was 3.01 (95% CI: 1.24–7.34, P = 0.015).Conclusion:The elevated level of serum VLDL-C was a significant and independent risk factor for ISR in diabetic CAD patients after coronary DES implantation.

Association of very Low-density Lipoprotein Cholesterol with All-cause and Cardiovascular Mortality in Peritoneal Dialysis

Background/Aims: Cardiovascular disease (CVD) is the leading cause of death in dialysis patients. Little is known about the relationship between very low-density lipoprotein cholesterol (VLDL-C) and cardiovascular mortality in these patients. Methods: A total of 1324 incident patients who began continuous ambulatory peritoneal dialysis (CAPD) therapy at our hospital between January 1, 2005, and September 30, 2014, with baseline serum VLDL-C values were investigated. The associations of the VLDL-C levels with all-cause and cardiovascular mortality were assessed. Results: The mean age of the cohort was 50.2 ± 14.8 years, and the mean VLDL-C level was 33.6 ± 18.0 mg/dl. One hundred sixty-five (12.5%) patients died during the study period. Multivariable models revealed that the high VLDL-C group was associated with significantly higher all-cause (HR, 2.08, 95% CI, 1.13 to 3.29, P = 0.002) and cardiovascular mortality (HR, 1.92, 95% CI, 1.18 to 4.29, P = 0.013) compared with the low VLDL-C group even after adjusting for various covariates. Using the VLDL-C level as a continuous variable, the hazard ratios (HRs) of all-cause and cardiovascular mortality associated with a 10-mg/dl increase in VLDL-C level were 1.12 (95% CI, 1.02 to 1.26, P = 0.025) and 1.11 (95% CI, 1.02 to 1.22, P = 0.029), respectively. VLDL-C was associated more strongly to all-cause (e.g., Akaike information criteria of 1990.205 vs. 1994.451) and cardiovascular (e.g., Akaike information criteria of 984.146 vs. 985.634) mortality than triglyceride (TG) levels. Conclusions: An elevated VLDL-C level is an independent risk factor for all-cause and cardiovascular mortality in peritoneal dialysis (PD) patients.

Hypolipidemic Activity of Prosopis cineraria L (Druce) Fruit Extract and Molecular Modeling Study with Farnesoid X Receptor (FXR)

Purpose: To investigate the hypolipidemic potential of the 70 % ethanol fruit extract of Prosopis cineraria (Fabaceae) (Et. PCF) in triton-induced hyperlipidemia in rats.Methods: Et-PCF was obtained by pulverizing whole dried fruits and extracting with 70 % ethanol. Adult Sprague Dawley rats were divided into six groups of six rats each. The groups were namely normal control, hyperlipidaemic control, standard drug-treated (simvastatin 4 mg/kg), and three Et-PCF (200, 400 and 600 mg/kg, respectively)-treated groups. Apart from normal control, all other groups received a single dose of triton (200 mg/kg, i.p.) exactly 30 min after a dose of the standard drug and Et-PCF for the induction of hyperlipidemia. Twenty four hours after trito injection, hyperlipidemia was confirmed by collecting blood samples from all the rats and testing for serum lipid profile. Antioxidant activity, in the form of inhibition of lipid peroxidation, was determined along with chromatographic analysis. Moreover, molecular docking study of â-sitosterol (active constitute of PCF) was performed with Farnesoid X receptor.Results: Triton-induced hyperlipidemia group showed significant increase in total cholesterol, low density lipoprotein cholesterol (LDL), very low density lipoprotein cholesterol (VLDL) , triglyceride, atherogenic index and decreased high density lipoprotein cholesterol (HDL), compared to normal control group. Et-PCF treated groups showed reduction in serum cholesterol, triglyceride, VLDL and LDL levels compared to triton treated control group. Extract at the dose of 200 mg/kg significantly reduce serum cholesterol (p &lt; 0.01) and serum LDL (p &lt; 0.01). At the dose level of 400 mg/kg and 600 mg/kg extract is effective to significantly reduce serum cholesterol (p &lt; 0.05), triglyceride (p &lt; 0.05), VLDL (p &lt; 0.05), LDL (p &lt; 0.05) and atherogenic index (p &lt; 0.05) and these results are almost equivalent to those of standard drug simvastatin. Furthermore, antioxidant activity, i.e., IC50 of Et-PCF was 58.33 ±g/ml. Molecular docking score of â-sitosterol for Farnesoid X receptor was -8.32 kcal/mol, suggesting excellent binding conformation of Et-PCF to receptor molecules.Conclusion: The findings suggest that Prosopis cineraria may be beneficial for preventing hyperlipidaemic complications by its anti-hyperlipidemic and antioxidant activities.Keywords: Prosopis cineraria, Anti-hyperlipidemic activity, Simvastatin, Triton, Docking studies, Farnesoid X receptor

Absence of adipose triglyceride lipase protects from hepatic endoplasmic reticulum stress in mice

Nonalcoholic fatty liver disease (NAFLD) is characterized by triglyceride (TG) accumulation and endoplasmic reticulum (ER) stress. Because fatty acids (FAs) may trigger ER stress, we hypothesized that the absence of adipose triglyceride lipase (ATGL/PNPLA2)-the main enzyme for intracellular lipolysis, releasing FAs, and closest homolog to adiponutrin (PNPLA3) recently implicated in the pathogenesis of NAFLD-protects against hepatic ER stress. Wild-type (WT) and ATGL knockout (KO) mice were challenged with tunicamycin (TM) to induce ER stress. Serum biochemistry, hepatic TG and FA profiles, liver histology, and gene expression for markers of hepatic lipid metabolism, ER stress, and inflammation were explored. Moreover, cell-culture experiments were performed in Hepa1.6 cells after the knockdown of ATGL before FA and TM treatment. TM increased hepatic TG accumulation in ATGL KO, but not in WT, mice. Lipogenesis and β-oxidation were repressed at the gene-expression level (sterol regulatory element-binding transcription factor 1c, fatty acid synthase, acetyl coenzyme A carboxylase 2, and carnitine palmitoyltransferase 1 alpha) in both WT and ATGL KO mice. Genes for very-low-density lipoprotein (VLDL) synthesis (microsomal triglyceride transfer protein and apolipoprotein B) were down-regulated by TM in WT and even more in ATGL KO mice, which displayed strongly reduced serum VLDL cholesterol levels. Notably, ER stress markers glucose-regulated protein, C/EBP homolog protein, spliced X-box-binding protein, endoplasmic-reticulum-localized DnaJ homolog 4, and inflammatory markers Tnfα and iNos were induced exclusively in TM-treated WT, but not ATGL KO, mice. Total hepatic FA profiling revealed a higher palmitic acid/oleic acid (PA/OA) ratio in WT mice, compared to ATGL KO mice, at baseline. Phosphoinositide-3-kinase inhibitor-known to be involved in FA-derived ER stress and blocked by OA-was increased in TM-treated WT mice only. In line with this, in vitro OA protected hepatocytes from TM-induced ER stress. Lack of ATGL may protect from hepatic ER stress through alterations in FA composition. ATGL could constitute a new therapeutic strategy to target ER stress in NAFLD.

Effects of Diacylglycerol on Glucose, Lipid Metabolism, and Plasma Serotonin Levels in Lean Japanese

Diacylglycerol (DAG)-rich oil has been suggested to suppress postprandial hyperlipidemia and promote negative caloric balance by increasing energy expenditure (EE), due to small intestine physiochemical dynamics that differ from triacylglycerol (TAG). We studied the effect of DAG on postprandial glucose/insulin metabolism by loading of carbohydrate with oil. Further, to reveal the mechanism for increased EE by DAG, we measured plasma serotonin, which is mostly present in the small intestine and mediates peripheral sympathetic thermogenesis. Randomized crossover study with 2-week wash-out interval between differing fat ingestion. Seven male, lean, Japanese students ingested DAG or TAG oil with 40 g of carbohydrate. Measurements of metabolic parameters were performed before and at 2, 4, and 6 h after fat ingestion. Plasma serotonin levels and cholesterol concentration in each lipoprotein were measured using high-performance liquid chromatography (HPLC). The substitution of DAG for TAG decreased very-low-density lipoprotein-cholesterol (VLDL-C) by 45.6% at 2 h, and decreased serum insulin by 41.3% at 4 h after ingestion. The incremental area under the curve (IAUC) for VLDL-C was positively correlated with the IAUC for insulin. Concurrently, DAG elevated plasma serotonin levels by 47.3% at 2 h, while TAG did not influence. This study indicates that the substitution of DAG for TAG suppresses the postprandial increase in serum VLDL-C and insulin. This study also demonstrates that DAG ingestion increases plasma serotonin, proposing a possible mechanism for a postprandial increase in EE by DAG.

Effect of ScrF I polymorphism in the 2nd intron of the HMGCR gene on lipid-lowering response to simvastatin in Chinese diabetic patients

Objective To investigate whether ScrF I polymorphism in the 2nd intron of the HMG-COA reductase gene (HMGCR) influences serum lipid levels and whether this polymorphism affects the efficiency of the cholesterol lowering HMG-CoA reductase inhibitor, simvastatin. Methods One hundred sixty-eight patients with type 2 diabetes mellitus (T2DM) prospectively received simvastatin as a single-agent therapy (20 mg day-1 p.o.) for 12 weeks. Serum lipid levels were determined before and after simvastatin treatment. Genotyping was performed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Results Subjects with the AA homozygotes had significantly higher serum very low-density lipoprotein cholesterol (VLDL-C) levels than those with the aa homozygotes. In addition, in 168 patients with T2DM who took 20 mg simvastatin, the VLDL-C lowering effect by simvastatin in subjects with the aa homozygotes was significantly lower than in those with the Aa heterozygotes and AA homozygotes. Conclusions Simvastatin treatment significantly decreased plasma lipids in all patients ( P < 0.01). Importantly, we demonstrate that ScrF I polymorphism of the HMGCR gene in patients with T2DM groups is associated with significant elevation of serum VLDL-C levels. Subjects with the AA homozygotes had significantly higher serum high VLDL-C levels than those with the Aa heterozygotes and aa homozygotes (AA: 2.18 ± 0.51; Aa: 2.04 ± 0.59, aa: 1.86 ± 0.43, P < 0.05 for comparison among three genotypes and P < 0.01 for difference between AA and aa). Furthermore, this polymorphism tends to show an enhanced response to an HMG-CoA reductase inhibitor in terms of the cholesterol-lowering effect. In 168 patients with T2DM who took 20 mg simvastatin, the VLDL-C lowering effect by simvastatin in subjects with the AA homozygotes was significantly lower than in those with the Aa heterozygotes and aa homozygotes (the reduction in serum VLDL-C levels; 37.03 ± 5.67 versus 28.97 ± 4.96, P < 0.01; 34.62 ± 5.87 versus 28.97 ± 4.96, P < 0.05). These results suggest that the HMGCR gene may serve as a modifier gene for hypercholesterolemia in Chinese diabetic patients.

Effects of postmenopausal hormone replacement and α-tocopherol on the lipid profiles and antioxidant status

Sixty-six postmenopausal women were randomly divided into three groups. The first group ( n=22) received transdermal oestradiol (0.05 g/day) for six months. Transdermal oestradiol was given during three weeks but was not given in the following week of each month during six months. In addition to the first group's therapy, medroxyprogesterone acetate (MPA; 10 mg/day, per orally) was administered to the second group ( n=22) for the last ten days. Vitamin E (600 mg/day, per orally) was given to the third group ( n=22) in addition to the first and second group therapy every day during six months. Total cholesterol, high density lipoprotein (HDL), very low density lipoprotein (VLDL) and low density lipoprotein (LDL) cholesterol, malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels of the three groups were measured at the beginning and at the end of therapy. In the transdermal oestradiol and transdermal oestradiol+MPA groups, post-treatment serum total, VLDL and LDL cholesterol levels decreased ( P<0.05) whereas HDL cholesterol level increased ( P<0.05). No significant difference was found in the levels of MDA, SOD and GSH-Px. In the third group, pre-treatment levels of total ( P<0.05), VLDL ( P<0.05), LDL cholesterol ( P<0.01) and MDA ( P<0.05) were high compared to post-treatment. Inversely, HDL cholesterol ( P<0.05) and vitamin E ( P<0.01) levels increased after the treatment. However, there was no significant difference in the levels of SOD and GSH-Px. In conclusion, in the post-menopausal period, because of the positive changes after hormone replacement plus vitamin E therapy, we suggest that hormone replacement and vitamin E combined therapy is effective in prevention of cardiovascular diseases.

Alterations of serum lipids and lipoproteins in breast cancer

Serum triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and very-low density lipoprotein (VLDL) cholesterol levels were quantified in Stage I and Stage IV breast cancer patients in order to evaluate the changes in serum lipids and lipoproteins in the early and advanced stages of the disease. When compared with data from age-matched healthy females, fasting serum triglycerides and VLDL cholesterol levels were found to be significantly increased and HDL cholesterol levels significantly decreased in patients with breast cancer. Further-more, a significant increase in triglycerides and VLDL cholesterol and decreases in total, HDL and LDL cholesterol levels were demonstrated in patients with Stage IV disease when compared to those with Stage I breast cancer. No significant difference was found in total and LDL cholesterol between Stage I breast cancer patients and healthy controls.

Serum cholesterol and lipoprotein concentrations in mothers during and after prolonged exclusive lactation

The effect of exclusive lactation on lipid levels was investigated by evaluating serum concentrations of total and lipoprotein cholesterol, triglyceride (TG), and apoprotein (apo) B in mothers during and after exclusive, prolonged lactation. Serum total cholesterol concentrations were measured at delivery (n = 195), at 2 (n = 165), 6 (n = 119), 9 (n = 74), and 12 months (n = 32) of lactation, and 2 months (n = 27) after ending this exclusive lactation. In a subgroup of 34 mothers, serum levels of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein 2 (HDL 2), HDL 3, and LDL apo B were determined at 2, 6, 9, and 12 months of lactation. The mean value of serum total cholesterol concentrations decreased from 6.2 ± 0.12 (SEM; n = 195) at delivery to 4.8 ± 0.1 mmol/L (n = 116) at 6 months of exclusive lactation ( P < .001). The average decrement in total cholesterol level was 0.80 mmol/L ( P < .001) from delivery to 2 months of lactation and 0.55 mmol/L ( P < .001) from 2 to 6 months of lactation, and levels were stable thereafter. In the 27 mothers who were exclusively breast-feeding their infants at 9 months of lactation and whose serum cholesterol levels were measured 2 months after the end of lactation, cholesterol levels increased rapidly to 5.7 ± 0.21 mmol/L ( P = .001). In the subgroup of 34 mothers who were examined more closely, the course just described was also true for serum TG, LDL and VLDL cholesterol, and LDL apo B levels. HDL 3 cholesterol levels were high at 2 and 6 months of exclusive lactation and decreased thereafter; in contrast, HDL 2 cholesterol levels were low at 2 months of lactation and slowly increased throughout the lactation period. We found that prolonged exclusive lactation reduced mothers' serum concentrations of total, LDL, HDL 2, and VLDL cholesterol and TG, which returned to their normal levels after the end of lactation.

Correction by insulin of disturbed TG-rich LP metabolism in rats with chronic renal failure.

To define the role of insulin in lipid disturbances of chronic renal failure, chronically uremic rats (U+) were supplemented by continuous insulin infusion over a 35-day experimental period and compared with control ad libitum-fed rats (C) and uremic rats without insulin (U). Uremic rats were characterized by hypoinsulinemia, an increase in both circulating very low-density lipoprotein (VLDL) and their cholesterol concentration, a normal hepatic triglyceride secretion rate (TGSR) determined with Triton WR 1339, and a low adipose tissue lipoprotein lipase (LPL) activity. Chronic insulin infusion at low rate (0.5 IU/24 h) to U+ rats normalized serum insulin (from 17.0 +/- 0.6 mU/l in U rats to 23.4 +/- 1.7 mU/l in U+ rats), serum VLDL triglycerides (from 804 +/- 65 to 410 +/- 36 mg/l), and serum VLDL cholesterol (from 43 +/- 8 to 16 +/- 3 mg/l). Hepatic TGSR decreased significantly after insulin treatment (from 0.58 +/- 0.03 to 0.44 +/- 0.03 mumol/min). Moreover, adipose tissue LPL was restored to normal by insulin supplementation (from 460 +/- 60 to 860 +/- 150 mU per total epididymal fat in U and U+ rats, respectively). Correction of the disturbed VLDL metabolism was associated with multiple actions of insulin including 1) a decrease of peripheral lipolysis, 2) a decrease of hepatic TGSR, and 3) an increase of adipose tissue LPL activity. Because cholesterol-rich VLDL are potentially atherogenic, their normalization with insulin treatment in this animal model suggests a viable area of investigation for the prevention of accelerated atherogenesis in chronic renal failure.