6-mo aerobic exercise intervention enhances the lipid peroxide transport function of HDL

During acute exercise, the concentration of oxidized high-density lipoprotein (HDL) lipids (ox-HDL) is reported to increase suggesting that HDL may function in decreasing the concentration of oxidized low-density lipoprotein (LDL) lipids. However, the effect of exercise intervention on the lipid peroxide transport function of HDL is unknown. A randomized controlled trial with sedentary women (N?=?161), aged 43–63, with no current use of hormone therapy, were randomized into a 6-month (mo) exercise group and a control group. During the 6-mo intervention, the concentration of ox-HDL increased in the exercise group by 5% and decreased in the control group by 2% (p?=?.003). Also, the ratio of ox-HDL to HDL-cholesterol increased by 5% in the exercise group and decreased by 1.5% in the control group (p?=?.036). The concentrations of cholesteryl ester transfer protein (CETP) and adiponectin did not change during the intervention. The concentration of serum triglycerides trended to decrease by 6% in the intervention group (p?=?.051). We found that the concentration of ox-HDL increased during the 6-mo aerobic exercise intervention, but the increase was not related to changes in the levels of CETP or adiponectin. These results, together with earlier studies, suggest that HDL has an active role in the reverse transport of lipid peroxides.     

氧化修饰高密度脂蛋白的研究进展

血浆高密度脂蛋白(HDL)与低密度脂蛋白(LDL)一样可以在体内外发生氧化修饰,引起其理化性质发生一系列的改变,如多不饱和脂肪酸过氧化,卵磷脂水解,蛋白质发生聚合或分解等.活体内HDL可能在动脉壁巨噬细胞、内皮细胞及中性粒细胞、单核细胞的作用下发生氧化修饰.氧化修饰HDL可能通过清道夫受体途径代谢.氧化修饰HDL产生多种致动脉粥样硬化作用.维生素E、C的摄入可能有助于防止脂蛋白的氧化.     

Total and Regional Fat and Serum Cardiovascular Disease Risk Factors in Lean and Obese Children and Adolescents

Objective: This study was conducted to evaluate the association of total and central adiposity with serum cardiovascular disease (CVD) risk factors in lean and obese Portuguese children and adolescents. Research Methods and Procedures: A total of 87 girls (13.2 ± 1.6 years old, 29.9 ± 6.4% body fat [mean ± SD]) and 72 boys (13.2 ± 1.6 years old, 20.8 ± 9.9% body fat) volunteered for the study. Whole‐body composition and fat distribution, from DXA and anthropometry, and serum lipids, lipoproteins, and apolipoproteins were evaluated. Results: The sum of three trunk skinfolds (STS) was highly correlated with total trunk fat mass measured by DXA (p < 0.001). Body mass index, DXA‐measured percentage of body fat, trunk fat mass, STS, and the waist‐to‐height ratio were generally found to be associated with triacylglycerol, the ratio of total cholesterol (TC) to high density lipoprotein‐cholesterol (HDL‐C), low density lipoprotein‐cholesterol (LDL‐C), and apolipoprotein B levels, (significant age‐adjusted r between 0.16 and 0.27, p < 0.05). Body mass index, STS, and the waist circumference were also associated with HDL‐C (p < 0.05), whereas no body composition variable significantly correlated with TC or apolipoproteins A‐I. The STS was significantly correlated with HDL‐C (p < 0.01), TC/HDL‐C (p < 0.05), and apolipoproteins A‐I (p < 0.05) independently of whole‐body fatness. Obese subjects (n = 73) had higher TC, LDL‐C, TC/HDL‐C, and apolipoprotein B than did non‐obese subjects (n = 86), and significant associations between central adiposity and some lipid variables (triacylglycerol and HDL‐C) were found in obese children and adolescents that were not present in leaner individuals. Discussion: DXA‐ and anthropometry‐based whole‐body and central fat measures are associated with serum CVD risk factors in Portuguese boys and girls. Obese children and adolescents have a poorer lipid profile than do their leaner counterparts. Trunk skinfolds, which are easy to obtain even in large samples, predict CVD risk factors to the same extent as DXA‐based variables, in some cases, independently of total fatness.     

Effects of Obesity and Body Fat Distribution on Lipids and Lipoproteins in Nondiabetic American Indians: The Strong Heart Study

Objectives: To examine the relationship between obesity and lipoprotein profiles and compare the effects of total obesity and central adiposity on lipids/lipoproteins in American Indians. Research Methods and Procedures: Participants were 773 nondiabetic American Indian women and 739 men aged 45 to 74 years participating in the Strong Heart Study. Total obesity was estimated using body mass index (BMI). Central obesity was measured as waist circumference. Lipoprotein measures included triglycerides, high‐density lipoprotei in (HDL) cholesterol, low‐density lipoprotein (LDL) cholesterol, apolipoprotein AI (apoAI), and apolipoprotein B (apoB). Partial and canonical correlation analyses were used to examine the associations between obesity and lipids/lipoproteins. Results: Women were more obese than men in Arizona (median BMI 32.1 vs. 29.2 kg/m²) and South Dakota and North Dakota (28.3 vs. 28.0 kg/m²), but there was no sex difference in waist circumference. Men had higher apoB and lower apoAI levels than did women. In women, when adjusted for center, gender, and age, BMI was significantly related to HDL cholesterol (r = ?0.24, p < 0.001). There was a significant but weak relation with apoAI (r = ?0.14 p < 0.001). Waist circumference was positively related to triglycerides (r = 0.14 p < 0.001) and negatively related to HDL cholesterol (r = ?0.23, p < 0.001) and apoAI (r = ?0.13, p < 0.001). In men, BMI was positively correlated with triglycerides (r = 0.30, p < 0.001) and negatively correlated with HDL cholesterol (r = ?0.35, p < 0.001) and apoAI (r = ?0.23, p < 0.001). Triglycerides increased with waist circumference (r = 0.30, p < 0.001) and HDL cholesterol decreased with waist circumference (r = ?0.36 p < 0.001). In both women and men there was an inverted U‐shaped relationship between obesity and waist with LDL cholesterol and apoB. In canonical correlation analysis, waist circumference received a greater weight (0.86) than did BMI (0.17) in women. However, the canonical weights were similar for waist (0.46) and BMI (0.56) in men. Only HDL cholesterol (?1.02) carried greater weight in women, whereas in men, triglycerides (0.50), and HDL cholesterol (?0.64) carried a large amount of weight. All the correlation coefficients between BMI, waist circumference, and the first canonical variable of lipids/lipoproteins or between the individual lipid/lipoprotein variables and the first canonical variable of obesity were smaller in women than in men. Triglycerides and HDL cholesterol showed clinically meaningful changes with BMI and waist circumference in men. All lipid/lipoprotein changes in women in relation to BMI and waist circumference were minimal. Discussion: The main lipoprotein abnormality related to obesity in American Indians was decreased HDL cholesterol, especially in men. Central adiposity was more associated with abnormal lipid/lipoprotein profiles than general obesity in women; both were equally important in men.     

Plasma paroaoxonase activities, lipoprotein oxidation, and trace element interaction in asthmatic patients

Paraoxonase (PON1) protects low and high-density lipoproteins (LDL and HDL) against oxidation induced by reactive oxygen species formation facilitated by iron (Fe) and copper (Cu) ions. Plasma PON1, arylesterase, oxidized LDL (Ox-LDL), Cu, Fe, thiobarbituric acid-reactive substances (TBARS), lipid, lipoprotein, and apolipoprotein profile in bronchial asthma were determined and the relations among these parameters in different steps of asthma were interpreted. A total of 58 individuals, 30 asthmatics and 28 controls, were included into the scope of this study. Plasma PON1, arylesterase, and TBARS levels were measured spectrophotometrically. Determination of plasma oxidized LDL, Cu, and Fe levels were performed by enzyme-linked immunosorbent assay, atomic absorption spectrophotometry, and the automated TPTZ method, respectively. Apo-A-1 and Apo-B levels were determined immunoturbidometrically. Plasma total cholesterol, triglyceride, and HDL cholesterol levels were enzymatically determined. Plasma LDL levels were estimated using the Fridewald formula. The average plasma PON1 and arylesterase activities in the group of patients were lower than those of the individuals in the control group, but there was no statistically significant difference found between them (p>0.05). No significant difference was found in plasma Apo-A-1, Apo-B, total cholesterol, triglyceride, HDL, and LDL concentrations between the control and patient groups (p>0.05). Plasma oxidized LDL (p<0.05), Cu (p<0.01), Fe (p<0.01), and TBARS (p<0.001) levels in patients with asthma were found to be significantly higher than for the control group. Increases in Cu, Fe, lipid peroxidation, and oxidized LDL levels supported by relative decreases in PON1 activities observed in asthmatic patients might be introduced as the striking findings as well as the possible potential indicators of this airway disease, the prevalence of which has increased dramatically over recent decades.     

Familial cholesteryl ester transfer protein deficiency is associated with triglyceride-rich low density lipoproteins containing cholesteryl esters of probable intracellular origin

The net transfer of core lipids between lipoproteins is facilitated by cholesteryl ester transfer protein (CETP). We have recently documented CETP deficiency in a family with hyperalphalipoproteinemia, due to a CETP gene splicing defect. The purpose of the present study was to characterize the plasma lipoproteins within the low density lipoprotein (LDL) density range and also the cholesteryl ester fatty acid distribution amongst lipoproteins in CETP-deficient subjects. In CETP deficiency, the conventional LDL density range contained both an apoE-rich enlarged high density lipoprotein (HDL) (resembling HDLc), and also apoB-containing lipoproteins. Native gradient gel electrophoresis revealed clear speciation of LDL subclasses, including a distinct population larger in size than normal LDL. Anti-apoB affinity-purified LDL from the CETP-deficient subjects were shown to contain an elevated triglyceride to cholesteryl ester ratio, and also a high ratio of cholesteryl oleate to cholesteryl linoleate, compared to their own HDL or to LDL from normal subjects. Addition of purified CETP to CETP-deficient plasma results in equilibration of very low density lipoprotein (VLDL) cholesteryl esters with those of HDL. These data suggest that, in CETP-deficient humans, the cholesteryl esters of VLDL and its catabolic product, LDL, originate predominantly from intracellular acyl-CoA:cholesterol acyltransferase (ACAT). The CETP plays a role in the normal formation of LDL, removing triglyceride and transferring LCAT-derived cholesteryl esters into LDL precursors.     

Proteinuria increases oxylipid concentrations in VLDL and HDL but not LDL particles in the rat

We previously established that proteinuria alters the apolipoprotein content of lipoproteins. This study was conducted to establish whether proteinuria also alters the concentrations of oxidized lipids within lipoprotein density fractions. To this end, we induced passive Heymann nephritis in Sprague Dawley rats and measured an array of alkaline-stable oxylipids in VLDL, LDL, and HDL particles. Proteinuria increased the total oxylipid amounts in the HDL and VLDL fractions. More importantly, these levels were increased when expressed per unit lipoprotein protein, indicating that the oxidized lipid load per particle was increased. Epoxides and diols increased approximately 2-fold in HDL and approximately 5-fold in VLDL, whereas LDL showed approximately 2-fold decreases. The hydroxyeicosatetraenoic acids and hydroxyoctadecadienoic acids (HODEs) increased >4-fold in HDL and >20-fold in VLDL, whereas LDL showed approximately 2-fold decreases in the HODEs. Therefore, nephrotic syndrome alters the lipoprotein oxylipid composition independently of an increase in total lipoprotein levels. These proteinuria-induced changes may be associated with the cardiovascular risk of lipoprotein oxidation.     

Cholesterol Forms and Traditional Lipid Profile for Projection of Atherogenic Dyslipidemia: Lipoprotein Subfractions and Erythrocyte Membrane Cholesterol

Atherogenic dyslipidemia characterized by abnormal changes in plasma lipid profile such as low high-density lipoprotein (HDL) and increased triglyceride (TG) levels is strongly associated with atherosclerotic diseases. We aimed to evaluate the levels of pro- and antiatherogenic lipids and erythrocyte membrane cholesterol (EMC) content in normo- and dyslipidemic subjects to investigate whether EMC content could be a useful marker for clinical presentation of atherogenic dyslipidemia. Low-density lipoprotein (LDL), HDL and their subfraction levels and erythrocyte lipid content were determined in 64 normolipidemic (NLs), 42 hypercholesterolemic (HCs) and 42 mixed-type dyslipidemic subjects (MTDs). Plasma atherogenic lipid indices [small–dense LDL (sdLDL)/less-dense HDL (LHDL), TC/HDL-C, TG/HDL-C and Apo B/AI] were higher in MTDs compared to NLs (p < 0.001). The highest sdLDL level was observed in HCs (p < 0.01). Despite a slight increase in EMC level in dyslipidemic subgroups, the difference was not statistically significant. A significant negative correlation, however, was observed between EMC and sdLDL/LHDL in HCs (p < 0.035, r = ?0.386). Receiver operating characteristic curves to predict sdLDL level showed that TG and EMC levels had higher area under curve values compared to other parameters in HCs. We showed that diameters of larger LDL and HDL particles tend to shift toward smaller values in MTDs. Our results suggest that EMC content and TG levels may be a useful predictor for sdLDL level in hypercholesterolemic patients.     

Differential channelling of liver lipids in relation to susceptibility to hepatic steatosis in two species of ducks

In the human, hepatic steatosis can be associated with an imbalance between synthesis, secretion and storage of hepatic lipids, and exhibits a genetic susceptibility. The effect of overfeeding on hepatic lipid channelling was investigated in two genotypes of ducks that differ in their susceptibility to fatty liver, i.e. the common duck, Anas platyrhynchos, and the Muscovy duck, Cairina moschata. Before overfeeeding, the Muscovy duck exhibited a lower subcutaneous adiposity and a higher muscular development, whereas hepatic composition was similar in both genotypes (>5% lipids and triglycerides accounting for 6–10% lipids). In the plasma lipoprotein profile, HDL predominated (5.5–7.8 g/l) over VLDL (0.09–0.25 g/l) and LDL (0.65–1.06 g/l). All lipid and lipoprotein concentrations were lower in the Muscovy duck. In response to overfeeding, the Muscovy duck exhibited a higher degree of hepatic steatosis (62 vs. 50% lipids), and a lower increase in adiposity and in the concentration of plasma triglycerides (6-fold vs. 10-fold) and VLDL (23-fold vs. 34-fold). Thus, certain genotypes may be more responsive to the dietary induction of fatty liver because of a less efficient channelling of hepatic lipids towards secretion into plasma and adipose storage, and the duck may represent a suitable model in which to study the development of hepatic steatosis and its pathogenesis.     

Cholesteryl ester transfer protein in metabolic syndrome

Objective: Low high‐density lipoprotein cholesterol (HDL‐C), hypertriglyceridemia, and small dense‐low density lipoprotein (LDL) are key components of metabolic syndrome (MS). Cholesteryl ester transfer protein (CETP) mediates the transfer of triglycerides (TGs) from TG‐rich lipoproteins to HDL and LDL particles in exchange for cholesteryl esters, leading to low HDL‐C and small dense‐LDL. The aim of this study was to investigate the role of CETP in subjects with MS. Research Methods and Procedures: In a cross‐sectional cohort of 234 middle‐aged men and 252 women randomly selected from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study, MS was diagnosed according to the National Cholesterol Education Program guidelines. CETP mass was determined by enzyme‐linked immunosorbent assay and LDL size‐by‐gradient polyacrylamide gel electrophoresis. Results: Men and women with MS had lower HDL‐C (45 ± 7 vs. 58 ± 13 and 48 ± 10 vs. 71 ± 14 mg/dL for men and women, respectively; p < 0.001 for all) and higher TG levels (222 ± 71 vs. 98 ± 54 and 167 ± 67 vs. 90 ± 35 mg/dL for men and women, respectively; p < 0.001 for all) than healthy subjects. LDL size was lower in subjects with MS (256 ± 11 Å vs. 267 ± 11 Å and 262 ± 10 Å vs. 273 ± 8 Å for men and women, respectively; p < 0.001 for all). CETP mass was higher in men with MS (1.87 ± 0.78 vs. 1.40 ± 0.65 μg/mL; p < 0.001) but not in women (1.74 ± 0.79 vs. 1.62 ± 0.62 μg/mL). CETP mass correlated inversely with LDL size in both men and women (r = ?0.19, p < 0.01 and r = ?0.13, p < 0.05 in men and women, respectively). Discussion: MS is associated with increased CETP mass in men. Increased CETP mass may be responsible for reduced HDL‐C and reduced LDL particle diameter in MS.     

Cholesterol-rich low density lipoproteins are also more oxidized

Cardiovascular diseases are accompanied by active oxygen species and organic free radical generation. The aim of this study was to examine the possibility of using oxidized low-density lipoprotein (oxLDL) as a new diagnostic biomarker. Epidemiological study in populations of Estonia (782 subjects) and Russia (1433 subjects) was carried out in 2007-2009. The screening procedure included standard epidemiological methods. Oxidative stress was assessed by measuring the level of oxLDL using immunoassay method. Positive correlation between the levels of oxLDL and LDL cholesterol was indicated in blood of patients from estonian (r = 0.61; P < 0.05) and russian (r = 0.56; P < 0.05) populations. In russian population oxLDL/HDL cholesterol ratio was higher in the groups with highest risk of atherosclerosis development or manifest coronary artery disease (CAD). Cholesterol-rich low density lipoproteins are also more oxidized. Estimation of oxLDL/HDL ratio may be used as an independent biochemical marker for atherosclerosis.     

Atherogenecity of LDL and unfavorable adipokine profile in metabolically obese, normal-weight woman

Objective: The relationship of visceral adiposity with adipocytokines and low‐density lipoprotein (LDL) particle distribution and oxidation in Asian metabolically obese, normal‐weight (MONW) individuals has not been evaluated. We aimed to investigate the association between visceral adiposity and adipocytokines and cardiovascular disease (CVD) risk factors in MONW Korean women with normal glucose tolerance. Methods and Procedures: We examined the metabolic characteristics of 135 non‐obese (BMI <25 kg/m²) women aged 25–64 years. Twenty‐five women (BMI <25 kg/m² and visceral fat adiposity (VFA) ≥100 cm²) were classified as MONW and 25 women (BMI <25 kg/m² and VFA <100 cm²), pair‐matched for age, weight, height, and menopausal status, as control group. Plasma lipid profiles and adipocytokines were evaluated in these two groups. Results: MONW subjects had higher systolic (P < 0.05) and diastolic blood pressure (P < 0.005) and higher concentrations of triacylglycerol (TG) (P < 0.005), insulin (P < 0.01), and free fatty acid (FFA) (P < 0.05) than control subjects. There was no significant difference between two groups in LDL‐cholesterol (LDL‐C) concentrations; however, MONW subjects had smaller LDL particles (P < 0.01) and higher concentrations of oxidized LDL (ox‐LDL) (P < 0.05) compared with controls. Moreover, MONW subjects had higher concentrations of tumor necrosis factor‐α (TNF‐α) (P < 0.05), interleukin‐6 (IL‐6) (P < 0.05) and leptin (P < 0.05), and lower plasma adiponectin concentrations (P < 0.05). Higher intake of saturated fat with lower ratio of polyunsaturated fatty acids (PUFAs) to saturated fatty acids (SFA) and lower fiber intake than normal subjects were found in MONW women. Discussion: We found an unfavorable inflammatory profile and a more atherogenic LDL profile in MONW female subjects even in the absence of a known CVD risk factors. Moreover, MONW consumed more saturated fat and less fiber than the control group.     

Quercetin up-regulates paraoxonase 1 gene expression with concomitant protection against LDL oxidation

Paraoxonase 1 (PON1) protects the oxidative modification of low-density lipoprotein (LDL) and is a major anti-atherosclerotic protein component of high-density lipoprotein (HDL). Quercetin, a ubiquitous plant flavonoid, has been shown to have a number of bioactivities and may offer a variety of potential therapeutic uses. We explored the roles of quercetin in the regulation of PON1 expression, serum and liver activity and protective capacity of HDL against LDL oxidation in rats. Compared to the pair-fed control group, feeding quercetin (10 mg/L) in the liquid diet for 4 weeks increased (a) hepatic expression of PON1 by 35% (p < 0.01), (b) serum and liver PON1 activities by 29% (p < 0.05) and 57% (p < 0.01), respectively, and (c) serum homocysteine thiolactonase (HCTL) activity by 23% (p < 0.05). Correspondingly, the lag time of low-density lipoprotein (LDL) oxidation was increased by >3-fold (p < 0.001) with plasma HDL from quercetin-fed group compared to the HDL from control group. Our data suggest that quercetin has antiatherogenic effect by up regulating PON1 gene expression and its protective capacity against LDL oxidation.     

Oxidized low-density lipoprotein (Oxidized LDL) and the risk of preeclampsia

Oxidative stress plays an important role in the pathophysiology of preeclampsia. In a case-control study of 99 women with preeclampsia and 99 controls, we assessed maternal plasma oxidized low-density lipoprotein (oxidized LDL) in relation to preeclampsia risk. Logistic regression procedures were used to derive odds ratios (OR) and 95 % confidence intervals (CI). Plasma oxidized LDL was determined using enzyme immunoassay. Maternal plasma oxidized LDL was significantly positively correlated with lipids in both cases and controls. After adjusting for nulliparity, pre-pregnancy body mass index, physical inactivity, family history of chronic hypertension and plasma vitamin C concentrations, women who had elevated oxidized LDL concentrations ( > or = 50 U/l) experienced a 2.9-fold increased risk of preeclampsia when compared with women having lower oxidized LDL concentrations (95 % CI 1.4-5.9). The risk of preeclampsia was markedly increased in women who had both elevated oxidized LDL and elevated triglyceride concentrations (OR=8.9, 95 % CI 3.1-26.2). Women with both elevated oxidized LDL and low vitamin C concentrations experienced a 9.8-fold increased risk of preeclampsia (95 % CI 3.0-32.2). Our results confirm the role of oxidative stress in the pathogenesis of preeclampsia. Prospective studies are needed to determine if elevated oxidized LDL concentrations can predict the occurrence of preeclampsia.     

Effect of dietary fiber of “Rihane” barley grains and azoxymethane on serum and liver lipid variables in Wistar rats

The aim of the present study is to evaluate the effects of diet enriched with dietary fiber of barley variety “Rihane” and azoxymethane on serum and liver lipid variables in male rats. Forty male rats were divided into four groups and fed on control diet or experimental diet that contained control enriched with dietary fiber of barley variety “Rihane”. Animals were injected with saline (controls) or azoxymethane (20 mg/kg body weight s.c.) at 7 and 8 weeks of age. The experimental diet significantly decreased cholesterol level compared with the control diet. Rats fed with BR diet significantly increased the serum high-density lipoprotein (HDL) cholesterol and significantly decreased low-density lipoprotein (LDL) cholesterol concentrations. The experimental diet decreased the atherogenic index (p < 0.05) compared with the control diet. Whereas the azoxymethane induced a significant increase of liver lipid, serum LDL and triglyceride concentrations, but it caused a significant reduction of HDL. Consequently, the ratio of HDL/TC decreased significantly compared with the control (p < 0.05). Accordingly, these results indicated that the diet enriched with dietary fiber of barley variety “Rihane” could be effective in decreasing the atherogenic risk factors in rats whereas the use of the azoxymethane as colon-specific carcinogen substance altered the lipid metabolism.     

Evaluation of serum lipids and high-density lipoprotein subfractions (HDL2, HDL3) in postmenopausal patients with breast cancer

Breast cancer patients are known to be at increased risk for developing other chronic diseases including cardiovascular disease. Studies by different investigators have shown a correlation between increased dietary fat or hypercholesterolemia and the occurrence of breast cancer. Since previous studies on lipoprotein subfractions in this type of cancer have been inconsistent, we evaluated the lipids and lipoprotein subfraction levels in postmenopausal patients with breast cancer in an attempt to identify the risk for the development of cardiovascular disease.The study included 132 patients, 56 of which were suffering from breast cancer, 32 from pancreatic and 44 age-matched controls. Total cholesterol (TC), triglycerides and lipoprotein fractions as well as TC/High density lipoprotein (HDL) and HDL2/HDL3 ratios were estimated by standard laboratory techniques.An increase in triglycerides and a decrease in HDL-cholesterol, especially in the HDL2 subfraction, were observed in patients with breast cancer as compared to the controls (P < 0.05). The maximum changes in TC, and HDL concentrations were observed in patients with advanced disease. Analysis of indexes of atherosclerosis (TC/HDL, and HDL2/HDL3 ratios) demonstrated that breast cancer patients had significantly higher TC/HDL ratio (6.44 ± 1.24) compared with controls (3.43 ± 0.57, p = 0.001), and patients with pancreatic cancer (3.79 ± 0.15, p = 0.027).The results have demonstrated an unfavourable lipid profile in untreated breast cancer patients with high atherosclerosis indexes. This observation is of great importance, considering the potential use of endocrine therapy that could result in further deterioration of lipid indexes. We propose the evaluation and monitoring of lipid profile prior and after the induction of hormonal therapy in breast cancer patients, as a routine in clinical setting. (Mol Cell Biochem 268: 19–24, 2005)     

Beneficial effects of alpha linolenic acid rich flaxseed oil on growth performance and hepatic cholesterol metabolism in high fat diet fed rats

The purpose of the study was to investigate the effect of flaxseed oil (FO), rich in alpha-linolenic acid (ALA) (18:3 n-3) on growth parameters and lipid metabolism of rats fed with high fat diet. High fat diet (HFD) resulted in significant alterations in hepatic lipids, increase in body weight gain and negative effect on lipoprotein metabolism. FO supplementation significantly lowered the increase in body weight gain, liver weight, plasma cholesterol, triglycerides, phospholipids, free fatty acids, high-density lipoprotein (HDL), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein (VLDL), LDL/HDL and TC/HDL ratio in HFD fed rats. FO significantly reduced the hepatic and plasma lipid levels indicating its hypolipidemic activity. On the other hand, oral administration of FO exhibited lower plasma lipoprotein profile as compared to HFD rats. Hepatic protection by FO is further substantiated by the normal liver histological findings in HFD fed rats. These data suggest that FO participate in the normal regulation of plasma lipid concentration and cholesterol metabolism in liver. No adverse effect of FO on growth parameters and plasma lipids in rats fed with fat-free diet. The results of the present study demonstrate that FO may be developed as a useful therapy for hyperlipidemia through reducing hepatic lipids, thereby proving its hypolipidemic activity.     

Amelioration of lipid abnormalities by α-lipoic acid through antioxidative and anti-inflammatory effects

Recent data have revealed that oxidative products and inflammatory mediators are increased in the insulin‐resistant states of obesity and type 2 diabetes mellitus (T2DM). Obese patients with impaired glucose tolerance (IGT) are at high risk for developing T2DM and have high incidence of dyslipidemia. α‐Lipoic acid (ALA) is a potent antioxidant with insulin sensitizing activity. However, it is not clear whether ALA is effective on lipid parameters in humans. This study has investigated 22 obese subjects with IGT (obese‐IGT), 13 of whom underwent 2‐week ALA treatment, 600 mg intravenously once daily. Before and after the treatment, euglycemic‐hyperinsulinemic clamps were used to measure insulin sensitivity. Meanwhile, plasma lipids, oxidative products, and chronic inflammatory markers were measured. After treatment of ALA in obese‐IGT patients, insulin sensitivity was improved, insulin sensitivity index (ISI) impressively enhanced by 41%. Plasma levels of free fatty acids (FFAs), triglyceride (TG), total cholesterol (T‐Chol), low density lipoprotein‐cholesterol (LDL‐Chol), small dense LDL‐Chol (sd‐LDL), oxidized LDL‐Chol (ox‐LDL‐Chol), very low density lipoprotein‐cholesterol (VLDL‐Chol) were all significantly decreased (P < 0.01). At the same time, both plasma oxidative products (malondialdehyde (MDA), 8‐iso‐prostaglandin) and inflammatory markers (tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6)) were remarkably decreased (P < 0.01), while adiponectin was increased (P < 0.01). There are significant negative correlations between ISI and plasma FFAs, sd‐LDL‐Chol, ox‐LDL‐Chol, MDA, 8‐iso‐prostaglandin, TNF‐α, and IL‐6, and positive correlations with HDL‐Chol and adiponectin in obese‐IGT patients. The results indicate that short‐term treatment with ALA can improve insulin sensitivity and plasma lipid profile possibly through amelioration of oxidative stress and chronic inflammatory reaction in obese patients with IGT.     

Paraoxonase 1 (PON1) and its relationship to lipid variables, age and gender in healthy volunteers

Recent studies implied that low-density lipoprotein (LDL) modified predominantly by oxidation or glycation, significantly contributes to the formation of atherosclerotic lesions. In contrast to oxidized LDL (ox-LDL), high-density lipoprotein (HDL) is able to prevent accumulation of ox-LDL in arterial walls. This antiatherogenic property of HDL is attributed in part to several enzymes associated with the lipoprotein, including HDL-associated paraoxonase 1 (PON1). In this study we analyzed PON1 arylesterase/paraoxonase activities in relation to serum lipid profile, gender and age in thirty clinically healthy Slovak volunteers. Our results showed that PON1 arylesterase and paraoxonase activities were lower in citrated plasma than in serum by 16.6% and 27.3%, respectively. Among serum lipoproteins, only HDL-cholesterol level showed significant positive correlation with PON1 arylesterase activity (p = 0.042). Likewise, we found a significant relationship between atherogenic index (AI = total cholesterol/HDL-cholesterol) and PON1 arylesterase activity (p = 0.023). No significant correlation could be demonstrated between PON1 paraoxonase activity and serum lipid profile, age or gender. Furthermore, it was found that PON1 paraoxonase/arylesterase activities were higher in women compared with both investigated activities in men, but these differences were not statistically significant. These results confirmed a positive correlation between HDL-cholesterol and PON1 arylesterase activity. Moreover, it was found out that PON1 paraoxonase activity is not influenced either by gender or by age. PON1 arylesterase activity was however affected by gender to a limited extent.     

New scoring system combining the FIB-4 index and cytokeratin-18 fragments for predicting steatohepatitis and liver fibrosis in patients with nonalcoholic fatty liver disease

Purpose: To establish a new scoring system as a noninvasive tool for predicting steatohepatitis and liver fibrosis in patients with nonalcoholic fatty liver disease (NAFLD).

Methods: A total of 170 patients histologically diagnosed with nonalcoholic steatohepatitis (NASH) (n?=?130) or nonalcoholic fatty liver (NAFL) (n?=?40) were enrolled. We analyzed receiver operating characteristic (ROC) curves and performed multivariate analysis to predict steatohepatitis and liver fibrosis.

Results: Multivariate analysis showed that cytokeratin-18 fragment (CK18-F) levels (≥278?U/L) (odds ratio [OR], 4.46; 95% confidence interval [CI], 1.42–14.00; p?=?0.010) and the FIB-4 index (≥1.46) (OR, 4.54; 95% CI, 1.93–29.50; p?=?0.004) were independently associated with prediction of NASH. We then established a new scoring system (named the FIC-22 score) for predicting NASH using CK18-F levels and FIB-4 index. The areas under the ROC curve (AUROCs) of the FIC-22 score and NAFIC score were 0.82 (95% CI, 0.75–0.89) and 0.71 (95% CI, 0.62–0.78) (p?=?0.044). Additionally, the AUROC of the FIC-22 score for predicting the presence of fibrosis (F?≥?1) was 0.78 (95% CI, 0.70–0.85).

Conclusions: In patients with NAFLD, the FIC-22 score had high predictive accuracy not only for steatohepatitis but also for the presence of liver fibrosis.