Increased Serum High-density Lipoprotein Research Articles

VLDL triglycerides inhibit HDL-associated paraoxonase 1 (PON1) activity: in vitro and in vivo studies

We analyzed, for the first time, both in vitro and in vivo, the effect of very low density lipoprotein (VLDL), or of pure triglycerides, on high-density lipoprotein (HDL)-associated paraoxonase1 (PON1) catalytic activities. Incubation of serum or HDL from healthy subjects with VLDL (0-330 μg protein/mL) significantly decreased serum PON1 lactonase or arylesterase activities by up to 11% or 24%, and HDL-associated PON1 lactonase or arylesterase activities by up to 32% or 46%, respectively, in a VLDL dose-dependent manner. VLDL (0-660 μg protein/mL) also inhibited recombinant PON1 (rePON1) lactonase or arylesterase activities by up to 20% or 42%, respectively. Similar inhibitory effect was noted upon rePON1 incubation with pure triglyceride emulsion. Bezafibrate therapy to three hypertriglyceridemic patients (400 mg/day, for one month) significantly decreased serum triglyceride concentration by 67%, and increased serum HDL cholesterol levels by 48%. PON1 arylesterase or paraoxonase activities in the patients' HDL fractions after drug therapy were significantly increased by 86-88%, as compared to PON1 activities before treatment. Similarly, HDL-PON1 protein levels significantly increased after bezafibrate therapy. Finally, bezafibrate therapy improved HDL biological activity, as HDL obtained after drug therapy showed increased ability to induce cholesterol efflux from J774A.1 macrophages, by 19%, as compared to HDL derived before therapy. We thus conclude that VLDL triglycerides inhibit PON1 catalytic activities, and bezafibrate therapy significantly improved HDL-PON1 catalytic and biological activities.

Liver X Receptor Agonist Modulation of Cholesterol Efflux in Mice With Intestine-Specific Deletion of Microsomal Triglyceride Transfer Protein

Previous work demonstrated that intestinal cholesterol absorption and regulated expression of intestinal Niemann-Pick C1-like 1 and ATP-binding cassette protein A1 are required for liver X receptor (LXR) agonist-mediated increases in high-density lipoprotein biogenesis. We re-examined those conclusions in mice with intestine-specific deletion of the microsomal triglyceride transfer protein (MTTP-IKO), where chylomicron formation is eliminated. MTTP-IKO mice demonstrated sustained ≈90% reduction in cholesterol absorption and >80% reduction in Niemann-Pick C1-like 1 expression, yet LXR agonist treatment increased serum high-density lipoprotein and upregulated intestinal ATP-binding cassette protein A1 expression. Hepatic lipogenesis and triglyceride content increased with LXR agonist treatment in both genotypes. Biliary cholesterol secretion was increased in MTTP-IKO mice without further increase upon LXR agonist administration. LXR agonist treatment caused a paradoxical increase in cholesterol absorption in MTTP-IKO mice and decreased fecal neutral sterol excretion, but to levels that still exceeded fecal neutral sterol excretion in LXR agonist-treated control mice. Finally, MTTP-IKO mice demonstrated indistinguishable patterns of increased cholesterol turnover and efflux after intravenous radiolabeled cholesterol administration, with or without LXR agonist treatment. Both intestinal and hepatic cholesterol efflux pathways are basally upregulated in MTTP-IKO mice. Moreover, LXR-dependent pathways modulate intestinal cholesterol absorption, transport, efflux, and high-density lipoprotein production independent of chylomicron assembly and secretion.

Whole and Particle-Free Diesel Exhausts Differentially Affect Cardiac Electrophysiology, Blood Pressure, and Autonomic Balance in Heart Failure–Prone Rats

Epidemiological studies strongly link short-term exposures to vehicular traffic and particulate matter (PM) air pollution with adverse cardiovascular (CV) events, especially in those with preexisting CV disease. Diesel engine exhaust is a key contributor to urban ambient PM and gaseous pollutants. To determine the role of gaseous and particulate components in diesel exhaust (DE) cardiotoxicity, we examined the effects of a 4-h inhalation of whole DE (wDE) (target PM concentration: 500 µg/m(3)) or particle-free filtered DE (fDE) on CV physiology and a range of markers of cardiopulmonary injury in hypertensive heart failure-prone rats. Arterial blood pressure (BP), electrocardiography, and heart rate variability (HRV), an index of autonomic balance, were monitored. Both fDE and wDE decreased BP and prolonged PR interval during exposure, with more effects from fDE, which additionally increased HRV triangular index and decreased T-wave amplitude. fDE increased QTc interval immediately after exposure, increased atrioventricular (AV) block Mobitz II arrhythmias shortly thereafter, and increased serum high-density lipoprotein 1 day later. wDE increased BP and decreased HRV root mean square of successive differences immediately postexposure. fDE and wDE decreased heart rate during the 4th hour of postexposure. Thus, DE gases slowed AV conduction and ventricular repolarization, decreased BP, increased HRV, and subsequently provoked arrhythmias, collectively suggesting parasympathetic activation; conversely, brief BP and HRV changes after exposure to particle-containing DE indicated a transient sympathetic excitation. Our findings suggest that whole- and particle-free DE differentially alter CV and autonomic physiology and may potentially increase risk through divergent pathways.

Hypolipidaemic effects and mechanisms of the main component of Opuntia dillenii Haw. polysaccharides in high-fat emulsion-induced hyperlipidaemic rats

The antihyperlipidaemic effects of ODP-Ia, one of the main components of Opuntia dillenii Haw. polysaccharides, were studied. Gavage administration of ODP-Ia was observed to significantly decrease serum lipid levels and to increase serum high-density lipoprotein cholesterol level in hyperlipidaemic rats. Similar suppressive patterns were also seen in hepatic total cholesterol and triglyceride levels. Moreover, the ODP-Ia administration significantly increased serum lecithin:cholesterol acyltransferase activity, increased the production of serum NO, inhibited hepatic HMG-CoA reductase activity, augmented serum and hepatic superoxide dismutase activities and decreased the serum and hepatic malondialdehyde contents in hyperlipidaemic rats. In addition, a histopathological examination revealed that ODP-Ia administration significantly suppressed inflammatory cell infiltration and the expression of VCAM-1. Together, these results indicate that ODP-Ia is a potential natural product for the treatment of hyperlipidaemia-related diseases by improving antioxidant levels, modulating the activities of enzymes involved in cholesterol metabolism, promoting the production of NO and suppressing the expression of VCAM-1, thereby suppressing lipid accumulation and inflammatory cell infiltration.

Curcumin preserves cognitive function and improve serum HDL in chronic cerebral hypoperfusion aging-rats

Background Chronic cerebral hypoperfusion is believed to be a critical factor on the occurrence of AD and VaD for which there is no effective therapy currently. It has been reported that high levels of circulating high density lipoprotein (HDL) can reduce the risk of cardiovascular disease. Although the relationship between cognitive function and serum lipids has captured attention, previous studies have shown ambiguous results. We investigated the effects of Curcumin on cognitive impairment and serum HDL levels and investigated whether increasing serum HDL levels ameliorate VAD-like cognitive deficits in rats induced by permanent occlusion of bilateral common carotid arteries (2VO).

Dissecting the role of peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) in colon, breast, and lung carcinogenesis

Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) is a promising drug target since its agonists increase serum high-density lipoprotein; decrease low-density lipoprotein, triglycerides, and insulin associated with metabolic syndrome; improve insulin sensitivity; and decrease high fat diet-induced obesity. PPARβ/δ agonists also promote terminal differentiation and elicit anti-inflammatory activities in many cell types. However, it remains to be determined whether PPARβ/δ agonists can be developed as therapeutics because there are reports showing either pro- or anti-carcinogenic effects of PPARβ/δ in cancer models. This review examines studies reporting the role of PPARβ/δ in colon, breast, and lung cancers. The prevailing evidence would suggest that targeting PPARβ/δ is not only safe but could have anti-carcinogenic protective effects.

HYPOLIPIDEMIC EFFECTS OF ORTANIQUE PEEL POLYMETHOXYLATED FLAVONES IN RATS WITH DIET-INDUCED HYPERCHOLESTEROLEMIA

ABSTRACT The cholesterol-lowering efficacy and possible mechanism of action of polymethoxylated flavones (PMFs) derived from Ortanique peel (PMFort) were evaluated in diet-induced hypercholesterolemic rats. Hypercholesterolemic and normal rats were fed diets containing PMFort and niacin for 49 days, after which several biochemical parameters were determined in the serum and organ samples. Diets containing 1.5% PMFort significantly reduced serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C) and triglyceride (TG) levels by 45%, 69%, 30% and 24%, respectively, and significantly increased serum high-density lipoprotein cholesterol (HDL-C) levels by 45% compared to the untreated hypercholesterolemic rats. Fecal cholesterol was also significantly increased (106%) by PMFort supplementation. Hepatic cholesterol was significantly reduced as well as the hepatic activity of HMG-CoA reductase in the PMFort supplemented group compared to the untreated hypercholesterolemic groups. The findings suggest that PMFort may be a potent hypocholesterolemic supplement that acts by reducing cholesterol synthesis as well as by increasing fecal cholesterol output. PRACTICAL APPLICATIONS The present study has several possible practical applications. The polymethoxylated flavones are found almost exclusively in citrus peel, which is usually discarded and is underutilized and contributes to solid waste in some countries. The results from this study as well as studies in the literature show that polymethoxylated flavones (PMFs) exhibit several important beneficial biological properties. The extract used in this study can be used to develop a wide range of nutraceutic and pharmaceutic products with hypocholesterolemic efficacy which may have possible applications as alternatives to lipid lowering drugs which display several adverse effects.

A prospective study on 6-year accumulative incidence rate of ischemic cardiovascular disease and related risk factors among the elderly male population under health care programme

To investigate the 6-year accumulative incidence rate of ischemic cardiovascular disease (ICVD) and its related risk factors. Baseline population was all from an elderly population with members all born before 1-1, 1938 and under health care programme. Data was recorded in a database of a hospital and baseline of subjects under research was aged >65 years. People that had had ICVD at baseline were excluded. Risk factors under research would include:age at the baseline study, gender, body mass index, systolic blood pressure, serum cholesterol level, serum triglyceride level, serum high-density lipoprotein level, serum triglyceride level, serum apolipoprotein A1 level, history of diabetes mellitus and cigarette smoking etc. Single factor analysis was carried out using person-years as time of study, then calculating the person-year incidence and the accumulative incidence rate at different levels related to baseline risk factors. Multivariate analysis was under Cox Proportional Hazards Regression Model. Baseline population included 2271 elderly men, with the 6-year cumulative prevalence rate of ICVD as 23.56%, and the person-year prevalence rate was 45.41‰. Single factor analysis showed that the ICVD events positively related to variables which including systolic blood pressure, body mass index, serum cholesterol level and serum triglyceride level, serum apolipoprotein A1 level, status of diabetes mellitus and cigarette smoking. The ICVD events negatively related to variables as serum high-density lipoprotein level and serum creatinine level. Results of multivariate analysis showed that high systolic pressure, diabetes mellitus, serum creatinine level, Body Mass Index were the main risk factors. The serum high-density lipoprotein level served as the main protective factor. The aged male population under health care programme was high in the ICVD prevalence rate, suggesting that programmes as controlling blood pressure, blood glucose, and increasing serum high-density lipoprotein levels were effective measures to decrease the ICVD events.

Hepatoprotective effects of almond oil against carbon tetrachloride induced liver injury in rats

This research aimed at evaluating the protective effects of almond oil against acute hepatic injury induced by carbon tetrachloride in rats. The study results showed that animals received almond oil prior to the administration of CCl 4 significantly decreased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) activities, and total cholesterol (TC), triglyceride (TG) and low density lipoprotein (LDL) content, and increased serum high density lipoprotein (HDL) content. Whereas, pre-treatment with almond oil markedly increased rat hepatic superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx) levels, and decreased the malondialdehyde (MDA) level. These results combined with liver histopathology demonstrated that almond oil has potent hepatoprotective effects, and could be developed as a functional food for the therapy and prevention of liver damage.

Cannabinoid 1 Receptor Blockade Reduces Atherosclerosis with Enhances Reverse Cholesterol Transport

A recent clinical study using coronary intravascular ultrasound showed that rimonabant, a cannabinoid 1 (CB1) receptor antagonist, significantly reduced total atheroma volume, suggesting that CB1 receptor blockade could be beneficial in anti-atherogenic therapy. The reverse cholesterol transport (RCT) system plays important roles in atherogenesis. We investigated whether CB1 receptor blockade could modulate atherogenesis in mice. Oral administration of rimonabant (8 mg/kg/day) to apolipoprotein E-deficient mice for 3 months significantly reduced the relative area of atherosclerotic lesions in the aorta (vehicle; 12.6+/-4.0% vs. rimonabant; 9.7+/-2.3, n=12 each, p<0.05) with an increase in serum adiponectin levels (15.6+/-2.3 microg/mL vs. 12.2+/-2.1, n=12 each, p<0.001), without affecting body weight or serum cholesterol levels. Rimonabant tended to increase serum high-density lipoprotein cholesterol (HDL-C) (p=0.05). The relative area of atherosclerotic lesions in the aorta correlated inversely with serum HDL-C levels (r=-0.45, n=24, p<0.05). Rimonabant upregulated the mRNA expression levels of various components of the RCT system on THP-1 cell-derived macrophages (scavenger receptor B1: 1.15+/-0.12 fold, n=6; p<0.05, ATP-binding cassette [ABC] transporter G1: 1.23+/-0.11 fold, n=6; p<0.01), but not ABCA1 (1.13+/-0.20 fold, n=6; p=0.13). CB1 receptor blockade reduced atherosclerosis in apoE-deficient mice through an increase in serum adiponectin levels and activation of the RCT system. CB1 receptor blockade may be therapeutically beneficial for atherogenesis by increasing the serum adiponectin level and enhancing of the RCT system.

Preventive effect of (−)epigallocatechin gallate on lipids, lipoproteins, and enzymes of lipid metabolism in isoproterenol‐induced myocardial infarction in rats

This article reports data on the preventive effect of (-)epigallocatechin gallate (EGCG) on lipid metabolism and lipoproteins in isoproterenol (ISO)-induced myocardial infarction (MI) in Wistar rats. The rats were induced MI by ISO (100 mg/kg) at an interval of 24 h for 2 days. EGCG (30 mg/kg) was given to rats as pretreatment for 21 days orally using an intragastric tube. EGCG significantly reduced the increased serum levels of cholesterol, triglycerides, and free fatty acids in the heart and serum phospholipids (PLs) in ISO-treated rats. It also significantly increased the reduced levels of heart PLs in ISO-induced rats. EGCG reduced the levels of serum low-density lipoprotein cholesterol and very low-density lipoprotein cholesterol and increased serum high-density lipoprotein (HDL)-cholesterol in ISO-treated rats. It also reduced the increased cholesterol/PL ratio and atherogenic index and significantly increased the reduced ratio of HDL-cholesterol/total cholesterol. Also EGCG significantly increased the reduced activity of lecithin cholesterol acyl transferase in ISO-treated rats. Thus, EGCG prevented the accumulation of lipids and altered the levels of lipoproteins in myocardial-infarcted rats.

Carbohydrate-restricted diets for obesity and related diseases: An update

Basic, clinical, and epidemiologic research on carbohydrate-restricted dietary patterns continues to grow, evaluating the impact of this way of eating on weight loss, obesity-associated comorbidities, and development of any adverse effects. Randomized, controlled, dietary weight loss trials conducted in adults in the past 2 years reinforce previous findings that carbohydrate-restricted diets (CRDs) promote weight loss while increasing serum high-density lipoprotein cholesterol, lowering serum triglycerides, and improving glucose homeostasis. Studies showing that reduction of dietary carbohydrate leads to reduced postprandial serum glucose and insulin levels have spurred further research on CRDs in patients with type 2 diabetes. Emerging interest into the effect of diet on endothelial function has spawned studies that are harnessing new technologies, such as flow-mediated vascular dilation, to gain insight into the impact of diet on long-term cardiovascular disease outcomes. Studies on the effect of a CRD on appetite, health-related quality of life, bone density and turnover, acid-base metabolism, and potassium equilibrium help clinicians better weigh the perceived risks of the diet with the recognized benefits. This review synthesizes important clinical and physiologic studies on CRDs published between January 2007 and May 2009.

Effect of Small Peptide Chelate Chromium on Growth Performance, Organ Development and Serum Traits in Spargue-Dawley Rats

The experiment was conducted to study the effect of supplementing Small Peptide Chelate Chromium (SPCr) in diets on growth performance, organ development and serum traits in Spargue-Dawley rats. Seventy two SD rats with initial body weight about (65±5 g) were randomly assigned to six dietary treatment, basal diet, basal diet supplemented with 100, 200, 500 or 1000 μg/kg Cr in the form of SPCr and 200 μg/kg Cr in the form of chromium picolinate (CrPic). Each treatment had 6 replicates. The duration of the study was 35 days. The results showed that: Supplementation of Cr with different types at low-level (below 500 μg/kg) increased daily gain and feed efficiency. Supplementation of 500 μg/kg SPCr increased ADG (p<0.05), decreased feed:gain ratio (p<0.05) compared with control group. Serum cholesterol and triglyceride was decreased(p<0.05) fed diets with SPCr at low-level. Supplementation of Cr with different types increased serum high density lipoprotein (p<0.05), also decreased serum glucose and insulin compared with control group. Addiction of Cr with different types increased the relative weights of liver (p<0.05). It was concluded that SPCr had effect to improve performance and serum lipids.

Effects of Copper Sulfate on Productive, Reproductive Performance and Blood Constituents of Laying Japanese Quail Fed Optimal and Sub-Optimal Protein

A (3X3) factorial design experiment was conducted to study the effect of three levels of crud e protein (16, 18 and 20%) and three levels of copper sulfate (0, 100 and 200 mg/kg diet) as a growth promoter on productive and reproductive performances, egg quality, blood serum constituents and economical efficiency of laying quail hens through 8 weeks. A total number of 270 hens and 135 males of Japanese quail at 8 weeks of age with nearly equal body weight and average rate of laying were randomly divided into 9 groups (30 hens and 15 males each). Each group of birds was sub divided into 3 replicates (10 hens and 5 males) and each replicate was housed in one wire cage. The results showed that the layer body weights at 12 or 16 weeks and weight gain at 12-16 and 8-16 weeks of age were significantly increased with increasing crude protein level from 16-18 or 20%, while there were no significant differences between the groups fed 18 and 20% crude protein throughout the experimental intervals and the whole period. Egg number, rate of laying and egg mass of laying quail hens increased with increasing crude protein at levels 16-18 or 20% (except at 12-16 week of age), while insignificant differences were found between the groups fed 18 and 20% crude protein throughout the experimental intervals and the whole period. Addition of copper sulfate at levels of 100 and 200 mg/kg to laying quail diets significantly improved egg number, rate of laying, egg mass and feed conversion ratio except at 8-12 weeks of age as compared with group non- supplemented with copper sulfate during the experimental period. The highest values of body weight and egg mass were recorded with 20 % protein plus 100 mg copper sulfate/kg diet, while, the best values of feed conversion and The highest values of egg number and rate of laying were recorded with 20 % protein plus 200 mg copper sulfate/kg diet from 8-16 weeks of age for quail layer as compared with other treatments. Laying quails hens fed diet contained copper sulfate levels significantly increased hatchability of fertile eggs percentage (except at 12 wks of age) as compared with those un-supplemented group. Various levels of crude protein or copper sulfate containing diets did not significantly affect on egg quality parameters, while egg yolk cholesterol was significantly decreased with increased copper sulfate levels. The highest values for total serum protein and serum albumin were recorded with experimental groups fed 18 or 20% protein levels compared with those received 16% protein diet, while serum cholesterol values were significantly decreased with increased crude protein. However, dietary copper sulfate supplementation reduced serum tri-glycerides, total cholesterol and low density lipoprotein cholesterol, but increased serum high density lipoprotein cholesterol. The best value of economic efficiency was recorded with laying quail hens fed 18% protein with 100 mg copper sulfate/kg diet compared with other treatment groups.

Androgen-Induced Progression of Arterial Calcification in Apolipoprotein E-Null Mice Is Uncoupled from Plaque Growth and Lipid Levels

Arterial calcification has prognostic significance for cardiovascular outcomes, but its pathogenesis remains unclear. Calcification increases with age, but its prevalence in men suggests hormonal influence. In this study we analyzed the effect of exogenous androgens on calcification of advanced atherosclerotic lesions in the arterial tree of gonadally intact 34-wk-old male and female apolipoprotein E-null mice. Testosterone (T) increased calcification 3- to 4-fold (P < 0.05) in lesions of the innominate artery and aortic sinus. A nonaromatizable androgen, dihydrotestosterone, also increased lesion calcification in the innominate artery (2.4-fold, P < 0.05) but not the aortic sinus. The androgen-induced effects were independent of sex and occurred despite corresponding reductions in plaque area, the latter correlating inversely with increased serum high-density lipoprotein cholesterol levels. Androgen-induced calcification in the innominate artery was observed with up-regulation of local androgen receptor (AR) expression in response to T and dihydrotestosterone for both males and females but neither androgen influenced innominate artery estrogen receptor (ER)-alpha or -beta expression in either sex. Conversely, T-induced calcification in the aortic sinus was associated with down-regulation of ERalpha but not ERbeta expression in both sexes, whereas androgen-induced AR expression was increased in female but decreased in male mice. This study demonstrates for the first time that calcification of advanced atherosclerotic lesions is an androgen-sensitive process and postulates potential roles for both AR- and ER-mediated pathways in androgen-induced vascular calcification. We demonstrate a novel direct link between vascular calcification and the major male hormone, T, uncoupled from conventional relationships with plaque growth and lipid levels.

Red mold rice prevents the development of obesity, dyslipidemia and hyperinsulinemia induced by high-fat diet

To investigate the influences of red mold rice (RMR) on obesity and related metabolic abnormalities. The 3T3-L1 cell line was used to examine the effects of RMR extracts on preadipocytes and on mature adipocytes. Both water and ethanol extracts of RMR had inhibitory effects on 3T3-L1 preadipocyte proliferation and differentiation. Water extracts of RMR enhanced the lipolysis activity in mature adipocytes, which negatively correlated with the triglyceride content within cells. RMR treatment did not affect heparin-releasable lipoprotein lipase activity in mature adipocytes. Furthermore, animal studies were carried out to explore the antiobesity effects of RMR. The control group of male Wistar rats were fed regular laboratory feed, whereas the other groups were fed the high-fat (HF) diet supplemented with lovastatin, rice or RMR (0.4 and 2%, w w(-1)). The relative caloric intakes of the control and HF groups were 3.34 and 4.85 kcal g(-1), respectively. After 6 weeks, rats treated with RMR at the 0.4 and 2% doses had lower weight gain and less fat pads mass accompanied with smaller fat cells than did the HF-diet rats. These effects probably resulted from an increase in the lipolysis activity of adipose tissue and a reduction in food/energy consumption. On the other hand, the RMR supplement significantly reduced serum total cholesterol, serum low-density lipoprotein (LDL) cholesterol, the ratio of LDL to high-density lipoprotein (HDL) cholesterol and serum insulin in the HF group. Moreover, the 2% RMR treatment significantly increased serum HDL cholesterol. This study reveals for the first time that RMR can prevent body fat accumulation and improve dyslipidemia. The antiobesity effects of RMR mainly derive from the lipolytic activity and mild antiappetite potency of RMR. In addition, extracts of RMR suppressed the proliferation and differentiation in 3T3-L1 preadipocytes, which might have contributed to the inhibition of new adipocyte formation or hyperplasia in adipose tissue.

HDL2 of Heavy Alcohol Drinkers Enhances Cholesterol Efflux From Raw Macrophages via Phospholipid‐Rich HDL2b Particles

Alcohol consumption is associated with increased serum high density lipoprotein (HDL) cholesterol levels and a decreased risk for the development of atherosclerosis. However, the effects of heavy alcohol intake on reverse cholesterol transport, one of the key anti-atherogenic processes related to HDL, are poorly known. The ability of total HDL as well as HDL(2) and HDL(3) subclasses to promote cholesterol efflux from (3)H-cholesterol-labeled RAW 264.7 macrophages was studied among 6 heavy alcohol drinkers and 6 controls. Distribution of HDL subclasses was analyzed by 4 to 30% native gradient gels. Serum phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) activities were analyzed among several other biochemical measures. Cholesterol efflux to HDL(2) of heavy drinkers was 22% (p = 0.025) higher relative to controls. The increase in HDL(2) phospholipids, with a concomitant 2-fold (p = 0.055) increase in large HDL(2b) particles, was associated with enhanced cholesterol efflux to HDL(2). Interestingly, the cholesterol efflux to HDL(3) did not differ between the 2 study groups. These findings may be partially explained by a decreased CETP activity (-26%, p = 0.037) and an increased PLTP activity (39%, p = 0.045) in heavy drinkers. The increased cholesterol efflux potential of HDL(2) is most likely an anti-atherogenic feature linked to heavy alcohol consumption. The cholesterol efflux and HDL phospholipids also associated strongly within the whole study group (r(s) = 0.910, p <or= 0.01) suggesting a common pathway of enhanced cholesterol efflux via enlarged phospholipid-rich HDL particles.

Characterizing the Lipid-Lowering Effects and Antioxidant Mechanisms of Tomato Paste

Lycopene is known to decrease cardiovascular risks. The objective of this study was to investigate the molecular mechanisms of tomato paste containing approximately 0.1% lycopene in regulating lipid metabolism and oxidation. Hamsters fed 3% or 9% tomato paste containing 0.2% cholesterol were subjected to total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), and triglyceride (TG) measurements. Our results showed reduced rates of serum TC and LDL levels due to 9% tomato paste were 14.3% and 11.3% respectively. Concentrations of 3% and 9% of tomato paste after 8 weeks of feeding significantly increased serum HDL levels, by 19.4% and 28.8% respectively. After ingestion of tomato paste for 8 weeks, the plasma malondialdehyde (MDA) levels significantly decreased, by 80.18% and 89.33% respectively, as compared to the cholesterol group. MDA and diene conjugation assays indicated the potent antioxidant activity of the tomato paste. The increased activities of superoxide dismutases (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), further supported the antioxidant effects of the tomato paste. Two dimension-gel electrophoresis (2-DE) analysis revealed that carbonic anhydrase III (CAIII) and adenylate kinase 2 (AK2) may be two important regulators involved in the anti-lipid and antioxidant effects of tomato paste, opening new insight into the nutritional value of tomato in public health promotion.

Peroxisome proliferator-activated receptor-β/δ (PPARβ/δ) ligands do not potentiate growth of human cancer cell lines

Ligands for peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) increase skeletal muscle fatty acid catabolism, improve insulin sensitivity, increase serum high-density lipoprotein cholesterol, elicit anti-inflammatory activity and induce terminal differentiation. Contradictory findings are also reported suggesting that PPARbeta/delta ligands potentiate tumorigenesis by increasing cell proliferation, by inhibiting apoptosis through phosphorylation of Akt and by increasing cyclooxygenase-2 (COX2) and vascular endothelial growth factor (VEGF) expression. The contradictory findings could be due to differences in the model system (cancer cell line versus in vivo), differences in cell culture conditions (with and without serum) or differences in ligands. The present study examined the effect of two different PPARbeta/delta ligands (GW0742 and GW501516) in human cancer cell lines (HT29, HCT116, LS-174T, HepG2 and HuH7) cultured in the presence or absence of serum and compared in vitro analysis with in vivo analysis. Neither PPARbeta/delta ligand increased cell growth or phosphorylation of Akt and no increase in the expression of VEGF or COX2 were detected in any cancer cell line in the presence or absence of serum. Similarly, liver, colon and colon polyps from mice administered these PPARbeta/delta ligands in vivo did not exhibit changes in these markers. Results from these studies demonstrate that serum withdrawal and/or differences in ligands do not underlie the disparity in responses reported in the literature. The quantitative nature of the present findings are inconsistent with the hypothesis that cancer cell lines respond differentially as compared with normal cells, and provide further evidence that PPARbeta/delta ligands do not potentiate tumorigenesis.

A dose‐response study of hormone replacement in young hypogonadal women: effects on intima media thickness and metabolism

Young hypogonadal women appear to have an increased risk of cardiovascular disease. We studied the influence of increasing doses of hormone replacement therapy (HRT) on markers of metabolism and vascular physiology. Nine-month sequential dose-ranging study. A total of 25 young hypogonadal women (Turner Syndrome, n = 14; 46,XX gonadal dysgenesis, n = 9), hypogonadotrophic hypogonadism (n = 2), mean age 31.9 years (range 18.5-42.2). All subjects sequentially received oral 17beta-oestradiol 1,2 and 4 mg daily in a cyclical formulation for 12 weeks each. Metabolic markers and vascular physiology measurements to assess intima media thickness (IMT); arterial stiffness: pulse wave velocity (PWV) and augmentation index (AIx); endothelial function: flow-mediated dilatation (FMD). Results Increasing doses of oestrogen resulted in a reduction in IMT (0.63 +/- 0.06 vs. 0.58 +/- 0.06 vs. 0.56 +/- 0.06 mm at 1 mg, 2 mg and 4 mg 17beta-oestradiol, respectively, P = 0.001). were similar in women with Turner Syndrome and normal karyotype. High-density lipoprotein (HDL) cholesterol concentrations increased (1.9 +/- 0.4 vs. 2.0 +/- 0.5 vs. 2.2 +/- 0.4 mmol/l, P = 0.001) and plasma glucose (4.8 +/- 0.4 vs. 4.7 +/- 0.3 vs. 4.6 +/- 0.6 mmol/l, P = 0.038) decreased slightly with the increasing dose of HRT. There was no correlation between the changes in IMT and HDL. Increasing HRT dose had no significant impact on blood pressure, weight, other lipid parameters, insulin, C-reactive protein, interleukin-6 and fibrinogen concentrations or FMD, PWV and AIx. Increasing doses of HRT result in a reduction in carotid IMT in young hypogonadal women, along with increased serum HDL and decreased plasma glucose. This study raises the possibility that exogenous oestrogen may be cardioprotective in young women, but this observation needs to be balanced against a prothrombotic effect which is predominant in postmenopausal women.