VLDL Concentrations Research Articles

Plasma apoE is Elevated in Metabolic Syndrome: Importance of Large Very Low Density and Low Density Lipoprotein Particles

Background: Apolipoprotein E (apoE) is carried by all major lipoprotein classes in plasma and is likely to contribute to the development of atherosclerosis. We set out to determine the extent to which plasma apoE is related to various VLDL, LDL and HDL subfractions in subjects with and without metabolic syndrome (MetS). Methods: Plasma lipids, lipoprotein subfractions (nuclear magnetic resonance spectroscopy) and plasma apoE were determined in 60 subjects with and 62 subjects without MetS (APOE e2/e2 carriers excluded). Results: Plasma apoE was higher in MetS, coinciding with increased total and large VLDL particles, as well as total LDL particles (p 0.30). Plasma apoE was unrelated to HDL particle concentration (p=0.88). Conclusions: Plasma apoE is elevated in MetS in conjunction with increased concentrations of (large) VLDL and LDL particles. These novel findings provide a rationale to explore whether preferential association of apoE with (large) VLDL and LDL could modify its influence on atherosclerosis development.

Lipoprotein subclass metabolism in nonalcoholic steatohepatitis

Nonalcoholic steatohepatitis (NASH) is associated with increased synthesis of triglycerides and cholesterol coupled with increased VLDL synthesis in the liver. In addition, increased cholesterol content in the liver associates with NASH. Here we study the association of lipoprotein subclass metabolism with NASH. To this aim, liver biopsies from 116 morbidly obese individuals [age 47.3 ± 8.7 (mean ± SD) years, BMI 45.1 ± 6.1 kg/m², 39 men and 77 women] were used for histological assessment. Proton NMR spectroscopy was used to measure lipid concentrations of 14 lipoprotein subclasses in native serum samples at baseline and after obesity surgery. We observed that total lipid concentration of VLDL and LDL subclasses, but not HDL subclasses, associated with NASH [false discovery rate (FDR) < 0.1]. More specifically, total lipid and cholesterol concentration of VLDL and LDL subclasses associated with inflammation, fibrosis, and cell injury (FDR < 0.1), independent of steatosis. Cholesterol concentration of all VLDL subclasses also correlated with total and free cholesterol content in the liver. All NASH-related changes in lipoprotein subclasses were reversed by obesity surgery. High total lipid and cholesterol concentration of serum VLDL and LDL subclasses are linked to cholesterol accumulation in the liver and to liver cell injury in NASH.

Obesity as a Risk Factor for Diabetes Mellitus in the Local Population of Pakistan

A worldwide epidemic exists with respect to diabetes mellitus because of increased rates of obesity. There is a significant correlation between obesity and insulin resistance and obesity causes the increase in the severity of the disease. The adipose tissues in the visceral region function as an endocrine organ that produces certain proteins with role in glucose homeostasis. The expression level of some of these proteins is increased in diabetes and can serve as specific marker of the disease. The study was performed to check the effect of various physical and biochemical parameters of obesity on the development and progression of diabetes mellitus. In our study the serum samples of diabetics were collected and were further categorized into two groups i.e. diabetic obese and diabetic non obese, on the basis of BMI, waist circumference and waist to hip ratio. The fasting blood sugar level, the total protein content, along with the complete lipid profile was performed. A marked increase in the total protein content and lipid profile was observed in diabetic obese as compared to diabetic non obese and control group. The results were found to be significant with p < 0.05. The lipid profile of diabetic obese was characterized by high cholesterol, LDL and VLDL concentration and low HDL concentration while that of control was characterizes by high HDL level and low cholesterol, LDL and VLDL level. The adipose secreted proteins whose expression is thought to increase in diabetes are studied. For this purpose the protein profile of serum was obtained on 10% SDS PAGE and the gels were stained with coomassie R-250 and silver salts. The proteins with exacerbated expression in diabetic obese individuals were studied. The expression of proteins such as leptin (16000 dalton), C reactive protein (25039 dalton), TNF alpha (25644 daltons), apolipoprotein E (34000 dalton), alpha 2 macroglobulin (163278 dalton) and apolipoprotein B (250000 dalton) was observed to be increased in diabetic obese as compared to diabetic non obese and control. There inflammation proteins secreted by adipose tissues cause the increase in the severity and progression of diabetes mellitus in the population.

Molecular cloning, expression profile and transcriptional modulation of two splice variants of very low density lipoprotein receptor during ovarian follicle development in geese (Anser cygnoide)

Very low density lipoprotein receptor (VLDLR)-mediated endocytosis of plasma lipoproteins into the ovary is essential for ovarian follicle development. Two splice variants of VLDLR have been identified in several species, yet little is known about their distinctive roles in ovarian developing follicles. In the present study, the full-length cDNAs of two splice isoforms of VLDLR were obtained from geese (Anser cygnoide) ovaries using the RACE method. The longer isoform (TypeI VLDLR) is 3141bp and contains five conserved structural domains, while the other (TypeII VLDLR) lacks 90bp encoding for the O-linked sugar domain. TypeII VLDLR was predominantly expressed in the ovary, with greater amounts of mRNA in theca and granulosa cells from early stages of follicle development but decreased during vitellogenesis. However, there was minimal expression of the TypeI VLDLR gene in theca cells and expression was almost undetectable in granulosa cells throughout follicle development. Yolk VLDL concentrations decreased as stage of development advanced while yolk triglyceride and cholesterol concentrations increased in a follicular size-dependent manner. The significant correlations between transcripts of TypeII VLDLR and yolk lipids supported its important role on yolk lipid deposition. In addition, in vitro experiments suggested that exogenous cholesterol, 25-hydroxycholesterol and mevinolin (a highly potent competitive inhibitor of HMG-CoA) treatment could significantly alter TypeII VLDLR gene expression in granulosa cells from both pre-hierarchical and pre-ovulatory follicles. Collectively, data from the present study indicate that TypeII VLDLR is more important for the transport of plasma lipoproteins into developing follicles than TypeI VLDLR, and provide new evidence about the influence of steroids in modulating VLDLR gene expression in ovarian cells.

Correlation of Body Mass Index and Waist Hip Ratio with lipid and hormone profile in women in menopausal transition

Introduction: Menopausal transition is a period characterised by psychic, somatic changes as well as changes in reproductive capabilities of a woman. It occurs as a consequence of ovarian’s function termination, and pertains to the periods of different meanings: perimenopause, menopause and postmenopause. Although there are numerous assessments of behaviour of the lipids and lipoproteins during menopausal transition, their relation to sexual hormones and body mass is still being assessed. The aim of this study is to determine the differences and connections between body mass index (BMI) and waist-hip ratio (WHR) and lipid and hormone profile among the assessees in premenopause, perimenopause and postmenopause.Methods: The assessment was done on 150 assessees divided in three groups of 50, such as: premenopause, perimenopause and postmenopause. The assessment included the following: interview, determination of BMI, WHR, and taking of blood sample and processing of hormone, lipid and lipoprotein concentration.Results: Based on the obtained results, it may not be concluded that BMI has a positive correlation with cholesterol and VLDL concentration in postmenopause, positive correlation with apo A in perimenopause and postmenopause, and positive correlation with Lp (a) and apo B in premenopause and perimenopause, while negative correlation with HDL and estradiol concentrations in premenopause.Conclusion: WHR has negative correlation with HDL concentration in premenopause and perimenopause, and a negative correlation with estradiol concentrations in premenopause.

Effects of Astrocaryum aculeatum Meyer (Tucumã) on Diet-Induced Dyslipidemic Rats.

An in vivo study was conducted to assess the effects of the consumption of Astrocaryum aculeatum Amazon Meyer (tucumã) in the treatment of diet-induced dyslipidemia in sedentary and exercised Wistar rats. With an average weight of 350 grams, 40 male rats were divided into 4 subgroups of 10. The sedentary control group (SCG) was fed with commercial feed, while the sedentary treatment group (STG) was fed with a ration of tucumã. In addition to the sedentary groups, two exercise groups were formed. The Exercised control group (ECG) was fed with commercial food and the exercised treatment group (ETG) was fed with a ration of tucumã. Body weight gain and food intake were monitored during the experiment. Plasma was analyzed for cholesterol, triglycerides, HDL-C, LDL-C, VLDL, total protein, glucose, insulin, and leptin concentrations. Our results show that the ECG group tended to consume more food, while the groups that were fed with tucumã pulp (STG and ETG) presented a greater tendency to gain body mass. ECG group showed a tendency towards a higher concentration of cholesterol in plasma, while STG and ETG presented higher absolute values for triglycerides and VLDL. No hypolipiemic effect was observed related to tucuma ingestion.

Assessment of Biochemical Parameters among Smokers and Tobacco Chewers to Ascertain Cardiovascular risk

Introduction: Cigarette smoking is one of the major cause and established risk factor of premature death due to respiratory and cardiovascular illness worldwide. Risk of coronary heart disease is increased by two-to four folds in smoking and tobacco chewing. Smoking and tobacco chewing leads to change in the concentration of serum total cholesterol, triglycerides, LDL, VLDL and HDL. In our present study, the main objective was to assess the blood lipid profile among smokers and tobacco chewers to ascertain cardiovascular risk in Nepal. Methods: It was a hospital based case control study carried out using data retrieved from the register maintained in the Department of Biochemistry of Institute of Medicine Teaching Hospital, Kathmandu, Nepal between 1st January, 2008 and 31st December, 2009. Of the 150 subjects enrolled in this study, 50 were current smokers, 50 were tobacco chewers and 50 were normal healthy controls. The variables collected were age, gender, total cholesterol, triglycerides, HDL, LDL, VLDL. The One way ANOVA was used to examine the statistical significant difference between groups. Post Hoc test LSD used for the comparison of means of control versus case groups. A p-value of &lt;0.05 (two-tailed) was used to establish statistical significance. Results: The mean values of serum total cholesterol (257.5±22.6 mg/dl), LDL (186.6±24.0 mg/dl), TG (139.4±39.8 mg/dl) were significantly higher in smokers when compared to controls. In contrast to that HDL (42.9±1.5 mg/dl) was lower when compared to controls (44.8±1.9mg/dl). The mean values for TG (141.5±34.9 mg/dl), total cholesterol (260.3 ±21.2 mg/dl), LDL (188.5±26.0 mg/dl) in tobacco chewers was significantly higher when compared to controls. Conclusions: The lipid profiles are raised in tobacco chewers and smokers which may lead to higher incidence of cardiovascular disease. Medical Journal of Shree Birendra Hospital; January-June 2013/vol.12/Issue1/29-31DOI: http://dx.doi.org/10.3126/mjsbh.v12i1.9089

Corticosterone regulation of ovarian follicular development is dependent on the energy status of laying hens

Glucocorticoids participate in the arousal of stress responses and trigger physiological adjustments that shift energy away from reproduction toward survival. Ovarian follicular development in avians is accompanied by the supply of yolk precursors, which are mainly synthesized in the liver. Therefore, we hypothesized energy status and hepatic lipogenesis are involved in the induction of reproductive disorders by glucocorticoids in laying hens. The results show that corticosterone decreased the laying performance by suppressing follicular development in energy-deficit state, rather than in energy-sufficient state. In corticosterone-treated hens, the suppressed follicular development was associated with the reduced availability of yolk precursor, indicated by the plasma concentration of VLDL and vitellogenin and the decreased proportion of yolk-targeted VLDL (VLDLy). Corticosterone decreased the expression of apolipoprotein B and apolipoprotein VLDL-II in the liver. A drop in VLDL receptor content and an increase in the expression of tight junction proteins occludin and claudin1 were also observed in hierarchical follicles. The results suggest corticosterone-suppressed follicular development is energy dependent. The decreased apolipoprotein synthesis and VLDLy secretion by liver are responsible for the decreased availability of circulating yolk precursor, and the upregulation of occludin and claudin expression further prevents yolk deposition into oocytes.

Omega-3 fatty acid ethyl ester supplementation decreases very-low-density lipoprotein triacylglycerol secretion in obese men

Dysregulated VLDL-TAG (very-low-density lipoprotein triacylglycerol) metabolism in obesity may account for hypertriacylglycerolaemia and increased cardiovascular disease. ω-3 FAEEs (omega-3 fatty acid ethyl esters) decrease plasma TAG and VLDL concentrations, but the mechanisms are not fully understood. In the present study, we carried out a 6-week randomized, placebo-controlled study to examine the effect of high-dose ω-3 FAEE supplementation (3.2g/day) on the metabolism of VLDL-TAG in obese men using intravenous administration of d5-glycerol. We also explored the relationship of VLDL-TAG kinetics with the metabolism of VLDL-apo (apolipoprotein) B-100 and HDL (high-density lipoprotein)-apoA-I. VLDL-TAG isotopic enrichment was measured using gas chromatography-mass spectrometry. Kinetic parameters were derived using a multicompartmental model. Compared with placebo, ω-3 FAEE supplementation significantly lowered plasma concentrations of total (-14%, P<0.05) and VLDL-TAG (-32%, P<0.05), as well as hepatic secretion of VLDL-TAG (-32%, P<0.03). The FCR (fractional catabolic rate) of VLDL-TAG was not altered by ω-3 FAEEs. There was a significant association between the change in secretion rates of VLDL-TAG and VLDL-apoB-100 (r=0.706, P<0.05). However, the change in VLDL-TAG secretion rate was not associated with change in HDL-apoA-I FCR (r=0.139, P>0.05). Our results suggest that the TAG-lowering effect of ω-3 FAEEs is associated with the decreased VLDL-TAG secretion rate and hence lower plasma VLDL-TAG concentration in obesity. The changes in VLDL-TAG and apoB-100 kinetics are closely coupled.

Effect of cholesterol on lipogenesis and VLDL–TG assembly and secretion in goose primary hepatocytes

To investigate how cholesterol induces hepatocytic steatosis, we investigated the effect of cholesterol on hepatic lipogenesis and the assembly and secretion of very-low-density lipoprotein-triglycerides (VLDL-TGs) in goose primary hepatocytes. We found that cholesterol at 20 μg/ml increased the concentrations of extracellular VLDL, intracellular cholesterol, and intracellular TGs, while cholesterol at 30 μg/ml had a reduced effect (p < 0.05). Additionally, cholesterol at 20 μg/ml, but not at 10 or 30 μg/ml, increased the extracellular TG concentration. Cholesterol increased the fatty acid synthase (FAS) enzyme activity in a dose-dependent manner. Incubation with cholesterol increased the mRNA level of genes involved in lipogenesis, including sterol regulatory element-binding proteins (SREBPs), FAS, acetyl-CoA carboxylase-α (ACCα), and liver X receptors. The mRNA level of the acyl-CoA: diacylglycerol acyltransferase 1 (DGAT1) gene changed in response to cholesterol treatment in a dose-dependent manner. Similar to the regulation of extracellular VLDL and intracellular TG accumulation, the mRNA levels of the microsomal triglyceride transfer protein, forkhead box O1, and DGAT2 increased with treatment with 10 or 20 μg/ml of cholesterol, but decreased with treatment with 30 μg/ml of cholesterol (p < 0.05). Cholesterol had no evident effect on the mRNA level of the apolipoprotein B gene. Incubation with cholesterol at 20 and 30 μg/ml increased the nuclear SREBP-1 protein level (p < 0.05) and the binding affinity of the nuclear SREBP-1 to ACCα SRE probes. In conclusion, cholesterol not only activates the transcription of genes involved in fatty acid synthesis and TG accumulation, but also activates the transcription of genes involved in the assembly and secretion of VLDL-TG in goose primary hepatocytes.

Effects of Cationic Hydroxyethyl Cellulose on Dyslipidemia in Hamsters

Cationic hydroxyethyl cellulose (cHEC) was supplemented in a high-fat diet to determine if this new soluble fiber had an effect on hypercholesterolemia and dyslipidemia associated with cardiovascular disease using Golden Syrian hamster as an animal model. Supplementation of 3-5% cHEC in a high-fat diet for 4 weeks led to significant weight gain reduction in hamsters. In addition, significant decreases in adipose and liver weights, concentrations of plasma total, VLDL, and LDL cholesterol, and hepatic lipids were shown. No significant improvements in glucose and insulin levels were observed with cHEC; however, a significant increase in plasma adiponectin and a decrease in leptin were observed. As compared with controls, 8% cHEC-fed hamsters had greater levels of mRNA for CYP7A1 (cytochrome P450 7A1; 2-fold of control; P < 0.05), CYP51 (lanosterol 14α-demethylase; 6-fold of control; P < 0.05), and LDLR (LDL receptor; 1.5-fold of control) in the liver. These findings suggest the possibility of the use of cHEC for cholesterol reduction and beneficial effects on the cardiovascular risk factors.

Lipid profile and lipoprotein(a) in chronic renal failure patients with and without hemodialysis

Objectives: Chronic renal failure (CRF) is complicated by characteristic dyslipidemias. CRF patients on hemodialysis have abnormalities in lipid profile and have a high incidence of cardiovascular diseases. Lipoprotein(a) [Lp(a)] is now considered as a novel cardiovascular risk factor and its level is increased in CRF patients with and without hemodialysis. We sought to evaluate the pattern of lipid profile including Lp(a) level in CRF patients with and without hemodialysis. Methodology: Study were divided into 3 groups, Group-I: healthy controls (30), Group-II: CRF patients who never undergone hemodialysis (30) and Group-III: CRF patients on hemodialysis for more than 6 months (30). We obtained serum samples from patients in the morning after an overnight fast and were analysed for total cholesterol (TC), triglycerides (TGs), HDL, LDL, Lp(a) using standard colorimetric assays on fully automated analyzer. VLDL concentration was calculated using Friedewald's Formula. Results: Among the various parameters tested triglyceride and VLDL levels were significantly higher in group-II and III as compared to controls (p 0.05) observed in total cholesterol and LDL levels in between healthy controls and CRF patients with & without hemodialysis. Lp(a) levels were significantly higher in group-II and III as compared to controls (p 0.05). There was no significant difference (p>0.05) observed between Lp(a) levels and lipid profile in male and female patients in control group and in CRF patients with and without hemodialysis. Conclusions: This study demonstrated that CRF patients with and without hemodialysis are at greater risk of development of dyslipidemias, characterized by hypertriglyceridemia, elevated VLDL and Lp(a) levels and decreased HDL levels. Total cholesterol and LDL cholesterol levels remain normal or decreased in these patients. Both male and female patients of CRF with and without hemodialysis have dyslipidemias without any discrimination of sex and it is not attenuated by the hemodialysis process.

Prediction of metabolic syndrome in women with polycystic ovary syndrome

To identify biochemical factors that serve as predictors for the metabolic syndrome (MetS) in patients with polycystic ovary syndrome (PCOS) and to investigate the value of adipocytokines in the prediction of metabolic syndrome. A total of 91 pre-menopausal women with PCOS diagnosed according to the Rotterdam consensus criteria were recruited as study subjects. Waist circumference, blood pressure, body mass index (BMI), fasting glucose, serum lipids, insulin, FSH, LH, E2, total testosteron, homeostatic model assessment-insulin resistance (HOMA-IR), serum leptin and adiponectin levels were evaluated for all patients. Of the 91 women with PCOS, 15 patients met the criteria for MetS. Body weight, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, and VLDL concentrations were significantly higher and HDL was significantly lower in women with PCOS+MetS compared with those with PCOS only. However, the level of LDL, FSH, LH, E2 and total testesterone was not significantly different between these two groups. Women with PCOS+MetS had significantly higher levels of leptin and HOMA-IR, and significantly lower levels of adiponectin compared to the women with PCOS only. In the multiple logistic regression model, the association between HOMA-IR and leptin, and MetS remained statistically significant (p=0.001 and 0.018), while the association between adiponectin and MetS was no longer statistically significant. Aside from the biochemical markers such as glucose, cholesterol and triglyceride, adipose tissue factors and insulin resistance are valuable parameters in the prediction of MetS in patients with PCOS.

Icosapent ethyl, a pure EPA omega-3 fatty acid: Effects on lipoprotein particle concentration and size in patients with very high triglyceride levels (the MARINE study)

Icosapent ethyl (IPE; formerly AMR101) is a high-purity prescription form of eicosapentaenoic acid ethyl ester. In the MARINE study we evaluated the efficacy and safety of IPE in patients with very high triglycerides (TG; ≥500 mg/dL) and previously demonstrated significant reductions in TG levels with no significant increases in low-density lipoprotein (LDL) cholesterol levels. In this follow-up, exploratory analysis, we report the effects of IPE on lipoprotein particle concentration and size. MARINE was a phase 3, multicenter, placebo-controlled, randomized, double-blind, 12-week study. Hypertriglyceridemic patients (N= 229) were randomized to three treatment groups: IPE 4 g/day, IPE 2 g/day, or placebo. Lipoprotein particle concentrations and sizes were measured by nuclear magnetic resonance spectroscopy. Compared with placebo, IPE 4 g/day significantly reduced median concentrations of large very-low-density lipoprotein (VLDL; -27.9%; P= .0211), total LDL (-16.3%; P= .0006), small LDL (-25.6%; P < .0001), and total high-density lipoprotein (HDL; -7.4%; P= .0063) particles and reduced VLDL particle size (-8.6%; P= .0017). In this patient population with TG ≥500 mg/dL, IPE did not significantly change the overall sizes of LDL or HDL particles. IPE 4 g/day significantly reduced large VLDL, total LDL, small LDL, and total HDL particle concentrations and VLDL particle size in patients with TG ≥500 mg/dL. Changes in VLDL particle concentration and size reflect the TG-lowering effects of eicosapentaenoic acid. The reduction in LDL particle concentration with IPE is novel among ω-3 therapies and is consistent with the previously reported reduction in apolipoprotein B and lack of LDL-C increase with IPE in patients with very high TG levels. NCT01047683.

Association between the Xba I polymorphism of APOB gene and plasma lipid level in Mexican patients with coronary artery disease.

Some studies, that consider polymorphisms of the apolipoprotein B (APOB) gene as risk factors for coronary artery disease (CAD), have reported discordant results. The aim of the present study was to search for associations between plasma lipid profiles with the DNA Xba I polymorphism of the APOB gene in CAD patients diagnosed by angiography (CAD+). In the present study we compared 114 Mexican patients (80 men and 34 women) with CAD+ and 132 control patients (59 men and 73 women) without evidence of ischemia or arterial damage (CAD-). The frequency of X+/X+ genotype of Xba I polymorphism, in CAD+ group, was 23% (26/114) compared with 8% (11/132) in the CAD- (OR 3.25, p = 0.002). The patients with X+/X+ for the Xba I genotype APOB gene had higher concentration of triglycerides (TG) and VLDL in plasma than CAD- (p< 0.05). The genotype X+/X+ in the CAD had an effect increasing the TG and VLDL plasma levels when compared with individuals with X-/X- and X-/X+ genotypes. The present study indicated that the X+X+ genotype of Xba I polymorphism is associated with CAD+ patients and high plasma levels of TG and VLDL, in the Mexican population.

Antisense inhibition of apoB synthesis with mipomersen reduces plasma apoC-III and apoC-III-containing lipoproteins

Mipomersen, an antisense oligonucleotide that reduces hepatic production of apoB, has been shown in phase 2 studies to decrease plasma apoB, LDL cholesterol (LDL-C), and triglycerides. ApoC-III inhibits VLDL and LDL clearance, and it stimulates inflammatory responses in vascular cells. Concentrations of VLDL or LDL with apoC-III independently predict cardiovascular disease. We performed an exploratory posthoc analysis on a subset of hypercholesterolemic subjects obtained from a randomized controlled dose-ranging phase 2 study of mipomersen receiving 100, 200, or 300 mg/wk, or placebo for 13 wk (n = 8 each). ApoC-III-containing lipoproteins were isolated by immuno-affinity chromatography and ultracentrifugation. Mipomersen 200 and 300 mg/wk reduced total apoC-III from baseline by 6 mg/dl (38-42%) compared with placebo group (P < 0.01), and it reduced apoC-III in both apoB lipoproteins and HDL. Mipomersen 100, 200, and 300 mg doses reduced apoB concentration of LDL with apoC-III (27%, 38%, and 46%; P < 0.05). Mipomersen reduced apoC-III concentration in HDL. The drug had no effect on apoE concentration in total plasma and in apoB lipoproteins. In summary, antisense inhibition of apoB synthesis reduced plasma concentrations of apoC-III and apoC-III-containing lipoproteins. Lower concentrations of apoC-III and LDL with apoC-III are associated with reduced risk of coronary heart disease (CHD) in epidemiologic studies independent of traditional risk factors.

Changes in lipoprotein subfraction concentration and composition in healthy individuals treated with the CETP inhibitor anacetrapib

We investigated the effects of the cholesteryl ester (CE) transfer protein inhibitor anacetrapib (ANA) on plasma lipids, lipoprotein subfraction concentrations, and lipoprotein composition in 30 healthy individuals. Participants (n = 30) were randomized to ANA 20 mg/day, 150 mg/day, or placebo for 2 weeks. Changes in concentration of lipoprotein subfractions were assessed using ion mobility, and compositional analyses were performed on fractions separated by density gradient ultracentrifugation. ANA 150 mg/day versus placebo resulted in significant decreases in LDL-cholesterol (26%) and apo B (29%) and increases in HDL-cholesterol (82%). Concentrations of medium and small VLDL, large intermediate density lipoprotein (IDL), and medium and small LDL (LDL2a, 2b, and 3a) decreased whereas levels of very small and dense LDL4b were increased. There was enrichment of triglycerides and reduction of CE in VLDL, IDL, and the densest LDL fraction. Levels of large buoyant HDL particles were substantially increased, and there was enrichment of CE, apo AI, and apoCIII, but not apoAII or apoE, in the mid-HDL density range. Changes in lipoprotein subfraction concentrations and composition with ANA 20 mg/day were similar to those for ANA 150 mg/day but were generally smaller in magnitude. The impact of these changes on cardiovascular risk remains to be determined.

Circulating Thyroid Hormones and Indices of Energy and Lipid Metabolism in Normal and Hormonally Induced Oestrus Cows

In a field study, circulating thyroid hormones, their free forms and indices of energy and lipid metabolism were measured in blood samples of 16 dairy cows expressing detectable oestrus signs. The cows were divided into two equal groups according to their days in milk (DIM=53-90 and DIM=100-150). In each group, 4 cows expressed the oestrus signs normally and the others were induced by hormone injection. Serum thyroxin (T4), free thyroxin (fT4), triiodothyronine (T3), free triiodothyronine (fT3), glucose, beta-hydroxybutyrate (BHB), non-esterified fatty acids (NEFA), triglyceride (TAG), cholesterol, very low density lipoproteins (VLDL-cholesterol), low density lipoproteins (LDL-cholesterol) and high density lipoproteins (HDL-cholesterol) were investigated. Comparison of all oestrus cows (normal or induced) between DIM groups (n=8 each) revealed lower levels of T4 (P=0.027) and T3 (P=0.022), but higher concentrations of fT4 (P=0.031) and fT3 (P=0.006) in the cows with lower DIM. Higher concentrations of TAG and VLDL (P=0.021) and cholesterol (P=0.046) as well as a tendency (P=0.074) for lower levels of BHB were other remarkable findings in cows with lower DIM. In cows with DIM=53-90, the normal oestrus cows had higher levels of T3 (P=0.044) as well as tendencies (P=0.083) for higher T4 and lower fT4 compared with induced cows. In cows with DIM=100-150, however, no significant difference was observed between the normal and induced oestrus cows. In conclusion, the cows that express oestrus signs normally may have better metabolic and thyroid hormone conditions compared to those that express heat by hormone injection. With progress in DIM, however, such differences may become less evident.

Effect of dietary energy source on deposition and fatty acid synthesis in the liver of the laying hen

1. This experiment was conducted to determine the effect of different dietary energy sources on hepatic lipid deposition and fatty acid synthesis in the layer's liver. 2. A total of 120 Lohmann Pink commercial layers were divided into three groups of 40 birds each and restricted-fed so that they had similar metabolisable energy intakes. Experimental diets were prepared as follows: (1) maize-soybean meal basal diet (CS) fed at 108 g/d, (2) soybean isolated protein plus lard diet (SL) fed at 63 g/d, (3) soybean isolated protein plus maize starch diet (SC) fed at 94·4 g/d. All feed intakes were limited so that the birds consumed similar quantities of the major nutrient daily; all the birds were fed 4 times/d. 3. Compared with chicks fed on the CS and SC, hepatic EE (ether extraction) and triglyceride of the SL group were increased significantly and the total of cholesterol and phospholipids was increased. However, there were no significant reductions in plasma VLDL and ApoB100 concentrations. 4. The birds fed on the maize starch diets up-regulated srebp-1c and chrebp mRNA transcription levels significantly. The maize starch diet also increased the activity of acetyl CoA carboxylase (ACC) and fatty acid synthase (FAS) significantly. However, the lard diet led to a decrease of ACC activity, but had no significant effect on FAS. 5. These results showed that dietary carbohydrates can induce hepatic lipid deposition by increasing the ACC and FAS activities and up-regulating the srebp-1c and chrebp mRNA transcription levels in the layer's liver much more readily than dietary fat, and layers fed on high carbohydrate diets tend to have more fatty livers.

Abstract 9515: NMR Spectroscopy Uncovers Important Atherogenic Lipoprotein Abnormalities in Nonalcoholic Fatty Liver Disease: The Insulin Resistance Atherosclerosis Study (IRAS).

Introduction: Nonalcoholic fatty liver disease may be the most frequent cause of chronically elevated transaminase levels in the general population. One of these inexpensive and routinely measured enzymes, alanine aminotransferase (ALT) is an independent predictor of future cardiovascular disease and diabetes. ALT has been associated with dyslipidemia, but the extent of this relationship is not well described. Hypothesis: Because to its advantage over conventional methods, we hypothesized that proton nuclear magnetic resonance (NMR) spectroscopy could be better for detecting atherogenic lipoprotein abnormalities in nonalcoholic fatty liver disease. Thus, we analyzed the relation of ALT to lipoproteins measured by NMR spectroscopy and conventional methods in non-diabetic participants in the IRAS. Methods: Cross-sectional analysis of lipoproteins and apolipoproteins in 912 non-diabetic participants in the IRAS. In fasting single fresh plasma samples, we measured plasma lipoproteins by conventional methods and NMR spectroscopy and apolipoprotein B (apo B) by immunoprecipitation. Insulin sensitivity was measured by the frequently sampled intravenous glucose tolerance test. Results: After adjusting for age, sex, race/ethnicity, and clinic, ALT was associated with triglycerides, LDL and HDL cholesterol, and apo B ( Table ). ALT had significant relationships with large VLDL, total LDL, IDL, small LDL, and large HDL particle concentrations plus VLDL, LDL, and HDL particle sizes. ALT remained associated with total LDL, IDL, and small LDL particle concentrations, LDL particle size, and apo B after the additional adjustment for waist circumference and insulin sensitivity. Conclusions: NMR spectroscopy uncovers a more extensive relationship between atherogenic lipoprotein abnormalities and ALT in non-diabetic individuals. These abnormalities could partially explain the relation of ALT to future cardiovascular disease.