Plasma Lipid Parameters Research Articles

The effect of dietary conjugated linoleic acid on the levels of lipids, cholesterol and iodothyronines in the blood of pigs

The aim of the investigation was to study the effect of dietary conjugated linoleic acid (CLA) on the concentrations of lipids, fatty acids and iodothyronines: thyroxine (T 4 ), triiodothyronine (T 3 ), reverse-triiodothyronine (rT 3 ), free T 4 (FT 4 ) and free T 3 (FT 3 ) in blood plasma of pigs. The experiment was carried out on 50 fatteners (average liveweight 50 kg) divided into 5 groups (5 gilts and 5 barrows per group). The pigs were fed a basal diet supplemented with 0, 0.5, 1, 1.5 and 2% of CLA isomers. Blood samples were collected from fatteners weighing 105 kg. Supplementation of the diet with CLA did not significantly affect lipid parameters in blood plasma. In comparison with gilts, a significantly higher concentration of triglycerides in barrows was found. In CLA-fed pigs, significant changes in the plasma fatty acid profile were noticed. The higher doses of CLA caused a significant increase in CLA and saturated fatty acids (SFA) with a concomitant decrease in monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids in blood plasma. Moreover, dietary CLA decreased the ∆9 desaturase index in a dose-dependent manner, probably as a result of

XbaI polymorphism of apolipoprotein B gene in a Tunisian population: alleles frequencies and relationship with plasma lipid parameters

Apolipoprotein B (Apo B) is a component of chylomicrons, low-density lipoproteins (LDL), very low density lipoproteins (VLDL), and intermediate-density lipoproteins (IDL) and is the ligand for the LDL receptor. Thereby, Apo B plays a central role in lipoprotein metabolism and in maintaining the normal homeostasis of serum cholesterol levels. Several Apo B restriction fragment length polymorphisms (XbaI, EcoRI, MspI) have been reported to be associated with variation in lipid levels, obesity and/or coronary artery disease. To date, no data are available on relationship between XbaI Apo B polymorphism and lipid levels in Tunisian population. Here, we report frequencies of the XbaI polymorphism of the Apo B gene and we assess the effect of this polymorphism on lipid and lipoprotein concentrations in Tunisian population. Blood samples from 296 Tunisian individuals (112 women and 184 men, aged 51.4+/-9.6 years), were analysed for total cholesterol, triglycerides, HDL-cholesterol and apolipoproteins A1 and B. In parallel, genotyping by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) was performed. The XbaI polymorphism was associated with differences in plasma cholesterol (p=0.04), triglyceride (p=0.02) and apolipoprotein A1 (p=0.004), individuals with the genotype X1X1 have the lowest mean levels and those with the genotype X2X2 have the highest, with the individuals heterozygous for the polymorphism having intermediate levels. According to sex, the XbaI polymorphism effect was only observed for triglyceride in men. Thus, the results demonstrate an influence of XbaI polymorphism of Apo B gene on serum total-cholesterol, triglycerides and apolipoprotein A1 concentrations among Tunisian population.

Apolipoprotein A5: An Emerging Paradigm For Genetic Associations And Interactions In Lipoprotein And Cardiovascular Research

For decades, apolipoprotein (Apo)E has reigned as the undisputed leader of lipoprotein genetics [1]. For many years, the impact of ApoE polymorphisms on plasma low-density lipoprotein (LDL)-cholesterol concentrations has been demonstrated in a reproducible fashion [2,3]. Moreover, several population studies have also shown how this genetic variability could be used to predict disease risk above and beyond traditional risk factors [4]. The interest in ApoE polymorphisms increased further when this major regulator of lipid metabolism was first implicated in the risk for neurological disorders and then for all types of chronic disorders (i.e., cancer and osteoporosis). Moreover, consistent with the knowledge that, for the population at large, the individual cardiovascular disease (CVD) risk is neither 100% genetic or environmental, ApoE has repeatedly shown significant gene–environment interactions modulating its association with plasma lipid parameters as well as CVD risk [5]. Thus, the ApoE gene has been considered as the paradigm of genetic associations and interactions within the lipid and CVD fields.

Identification and Synthesis of a Novel Selective Partial PPARδ Agonist with Full Efficacy on Lipid Metabolism In Vitro and In Vivo

The aim was to identify a novel selective PPARdelta agonist with full efficacy on free fatty acid (FFA) oxidation in vitro and plasma lipid correction in vivo. Using the triple PPARalpha,gamma,delta agonist 1 as the structural starting point, we wanted to investigate the possibility of obtaining selective PPARdelta agonists by modifying only the acidic part of 1, while holding the lipophilic half of the molecule constant. The structure-activity relationship was guided by in vitro transactivation data using the human PPAR receptors, FFA oxidation efficacy performed in the rat muscle L6 cell line, and in vivo rat pharmacokinetic properties. Compound 7 ([4-[3,3-bis-(4-bromo-phenyl)-allylthio]-2-chloro-phenoxy]-acetic acid) was identified as a selective, partial agonist with good oral pharmacokinetic properties in rat. Chronic treatment of high fat fed ApoB100/CETP-Tgn mice with 7 corrected the plasma lipid parameters and improved insulin sensitivity. These data suggest that selective PPARdelta agonists have the potential to become a novel treatment of dyslipidemia.

The Effect of Varied Dietary Grains on Plasma Lipid Profiles, Gut Transit Time, and Aorta Histopathology in Experimental Rats

This study was designed to investigate the influence of natural brown and black rice consumption on plasma lipid parameters, transit time, and thickness of the aortic wall in rats fed different combinations of grains. Fifty male rats were divided into five groups and raised for eight weeks with diets containing white rice (WR), white rice and brown rice (WRBR), white rice and black rice (WRBL), brown rice and black rice (BRBL), or wheat flour (WH). Gut transit time was the shortest in the BRBL group, and was longer in the order of WRBL, WRBR, WR, and WH group. Plasma lipid profiles differed significantly according to the grain combination. The BRBL group had the lowest levels of triglyceride (TG), total cholesterol (T-C), and low-density lipoprotein cholesterol (LDL-C), and the highest plasma high-density lipoprotein cholesterol (HDL-C) concentration among all groups. The aortic wall thickness hatro for body weight was lower in rats in order of BRBL, WRBR, WH, WRBL, and WR group. In conclusion, black rice and brown rice have anti-atherogenic effects by decreasing plasma lipide profiles and attenuating the thickness of the aortic wall.

Association between plasma lipid parameters and APOC3 genotypes in Brazilian subjects: Effect of gender, smoking and APOE genotypes

Background APOC3 polymorphisms were associated with lipid parameters and coronary artery disease in several populations but not all. Considering the multifactorial inheritance and environmental factors that underlie the determination of triglyceride (TG) and HDL-C levels, the aims of the present study were to perform association analyses of APOC3 polymorphisms and these lipids in a southern Brazilian population of European descent to investigate possible interactions with other genetic and/or environmental factors. Methods Six hundred and seventy-three subjects participated in the study. – 482C > T , – 455T > C and 3238C > G polymorphisms genotyping were carried out by PCR followed by restriction enzyme digestion. Results In female subjects the APOC3– APOE genotype combinations had a significant effect on triglyceride levels (ANOVA, P = 0.009). Post hoc analysis showed that the observed differences were between APOC3 S ⁎ 2 carriers and S ⁎ 1S ⁎ 1 homozygotes in individuals with an APOE ⁎ 3/3 genotype (Tukey HSD post hoc test, P = 0.027). In APOE ⁎ 3/ ⁎ 3 subjects, the raising effect of APOC3 S ⁎ 2 allele on TG concentrations was more pronounced in female smokers (+ 59.4%) than in nonsmokers (+ 18.8%, P of S ⁎ 2–smoking interaction = 0.009). Among APOE ⁎ 3/ ⁎ 3 subjects, male carriers of the less common alleles − 482T and − 455C had significant lower levels of HDL-C compared to homozygotes − 482C/ C and − 455T/T ( P = 0.02 and P = 0.006, respectively). Conclusion APOC3 polymorphisms were associated with lipid variables, but the magnitude of these associations was modulated by additional genetic, biologic and/or environmental factors.

Pravastatin in HIV-Infected Patients Treated with Protease Inhibitors: A Placebo-Controlled Randomized Study

Purpose: The objectives of the study were to assess the effects of pravastatin on plasma HIV RNA, lipid parameters, and protease inhibitor (PI) concentrations in patients treated with PI-containing regimens and with total cholesterol (TC) ⩾5.5 mmol/L.Method: A clinical trial including patients randomized to receive pravastatin or matching placebo for 12 weeks was implemented. Results: Twelve patients were included in the pravastatin group and 9 in the placebo group. At week 12 (W12), no patient had experienced virological failure. Between week 0 (W0) and W12, the median differences for TC were –1.4 mmol/L in the pravastatin group and +0.2 mmol/L in the placebo group (p = .005); for LDL, they were –1.0 mmol/L and +0.3 (p = .007), respectively. A significant decrease of the PI concentration (12 hours after administration) ratio W12 – W0/W0 was noticed in the pravastatin group (–0.2 [interquartile range, –0.3 to –0.1] as compared with the placebo group (0.1 [IQR, 0.0 to 0.3]) (p = .03). When the study was restricted to patients treated with lopinavir/ritonavir, a decrease from 3.8 μg/mL at baseline to 2.9 μg/mL at W12 was noticed in the pravastatin arm (p = .04) but not in the control arm (p = 1.00). No clinical adverse event reached a severity of grade 3. Conclusion: We observed in this study that the use of pravastatin in PI–treated patients was not associated with major change in the plasma HIV RNA on 12 weeks of follow-up. However, we found a trend of decrease of the trough PI concentration at W12, suggesting a possible drug–drug interaction of pravastatin on PI metabolism.

Upregulation of liver VLDL receptor and FAT/CD36 expression in LDLR−/− apoB100/100 mice fed trans-10,cis-12 conjugated linoleic acid

This study explores the mechanisms responsible for the fatty liver setup in mice fed trans-10,cis-12 conjugated linoleic acid (t10c12 CLA), hypothesizing that an induction of low density lipoprotein receptor (LDLR) expression is associated with lipid accumulation. To this end, the effects of t10c12 CLA treatment on lipid parameters, serum lipoproteins, and expression of liver lipid receptors were measured in LDLR(-/-) apoB(100/100) mice as a model of human familial hypercholesterolemia itself depleted of LDLR. Mice were fed t10c12 CLA over 2 or 4 weeks. We first observed that the treatment induced liver steatosis, even in the absence of LDLR. Mice treated for 2 weeks exhibited hypertriglyceridemia with high levels of VLDL and HDL, whereas a 4 week treatment inversely induced a reduction of serum triglycerides (TGs), essentially through a decrease in VLDL levels. In the absence of LDLR, the mRNA levels of other proteins, such as VLDL receptor, lipoprotein lipase, and fatty acid translocase, usually not expressed in the liver, were upregulated, suggesting their involvement in the steatosis setup and lipoprotein clearance. The data also suggest that the TG-lowering effect induced by t10c12 CLA treatment was attributable to both the reduction of circulating free fatty acids in response to the severe lipoatrophy and the high capacity of liver to clear off plasma lipids.

Cross-sectional Comparison of Fasting Lipids in Normoglycemic Patients With Schizophrenia During Chronic Treatment With Olanzapine, Risperidone, or Typical Antipsychotics

We compared fasting lipids and other metabolic parameters in 211 normoglycemic patients meeting the DSM-IV diagnosis of schizophrenia or schizoaffective disorder undergoing continuous treatment with olanzapine, risperidone, or typical antipsychotics for at least 1 year. Blood samples were obtained after an 11-hour (+/-1 h) observed fast. Olanzapine-treated patients had significantly higher mean fasting triglyceride levels (2.3 +/- 1.8 mmol/L) than risperidone- (1.7 +/- 0.9 mmol/L, P = 0.022), but not typical antipsychotic-treated patients (1.8 +/- 1 mmol/L). There were no significant differences in total low-density (LDL-C) or high-density lipoprotein cholesterol levels. Apolipoprotein-B and very low density lipoprotein cholesterol levels were significantly higher in the olanzapine- versus risperidone-treated patients, but there were no significant differences between olanzapine- and typical antipsychotic-treated patients. Treatment groups did not differ significantly in LDL particle size, the prevalence of an "atherogenic" lipid profile, or estimated insulin sensitivity. Although interpretation of this study is limited by the cross-sectional study design, it provides additional insight concerning the relationship between antipsychotic use and plasma lipid parameters in this population.

Effects of vitamin E on oxidative stress and atherosclerosis in an obese hyperlipidemic mouse model

Vitamin E is a natural antioxidant that has been used in animal and human studies to determine its potential in reducing cardiovascular risk; however, a detailed study in an established obese model of atherosclerosis has yet to be performed. In our current study, we show that obesity and hyperlipidemia cause a synergistic, age-related increase in urinary isoprostane levels in mice deficient in both leptin and low-density lipoprotein receptor (ob/ob;LDLR −/−). Based upon this observation, we hypothesized that vitamin E supplementation would induce potent antiatherogenic effects in this model. Lean and obese LDLR −/− mice were provided vitamin E (2000 IU/kg) in a Western-type high-fat diet for 12 weeks. Plasma lipid parameters, such as total cholesterol (TC), triglyceride (TG) and free fatty acid, were significantly higher in obese mice compared to lean mice at baseline ( P<.001). Western-type diet (WD) feeding caused an increase in TC levels in all groups ( P<.001); however, TG ( P<.001) and free fatty acid ( P<.01) were elevated only in lean mice following WD feeding. Vitamin E supplementation neither influenced any of these parameters nor reduced urinary isoprostanes in lean or obese mice. Vitamin E supplementation in ob/ob;LDLR −/− mice resulted in a trend toward a reduction in atherosclerotic lesion area ( P=.10), although no differences in lesion area were noted in lean LDLR −/− animals. These data provide evidence that vitamin E supplementation is not sufficient to reduce extreme elevations in systemic oxidative stress due to hyperlipidemia and obesity and, thus, may not be cardioprotective in this setting.

Apolipoprotein E polymorphism in the Tunisian population: Frequency and effect on lipid parameters

Objectives: We determined the frequencies of apolipoprotein E (apo E) gene alleles and examined the association between apo E polymorphism and lipid parameters in a sample of the Tunisian population. Design and methods: Apo E polymorphism was investigated using PCR, and plasma lipid parameters were measured in 122 men and 111 women aged 35 to 87 years. Results: The allele frequencies were ε2: 7.3%, ε3: 84.6%, and ε4: 8.1%. Apo E polymorphism was associated with significant differences ( P < 0.001) in total cholesterol, apo B and LDL cholesterol in both men and women. ε2 carriers had the lowest mean total cholesterol, apo B and LDL-C concentrations, and subjects with the ε4 allele had the highest levels. Triglycerides levels increased with the ε4 allele, but this did not reach statistical significance. These results remained unchanged after adjustment for age, body mass index, sex, hypertension, diabetes and smoking. However, in obese subjects (BMI > 30 kg/m 2), TG concentrations were significantly lower in individuals homozygous for the ε3 allele compared to those with the alleles ε2 or ε4. Conclusion: In this sample of the Tunisian population, the distribution of apo E gene alleles is similar to that observed in Southern European populations with low prevalence of the ε4 allele. Variations in the apo E gene play a role in determining plasma lipid levels. These data also suggest that effects of apo E alleles on lipids levels are partly dependent on environmental variables such as BMI. These findings highlight the importance of the gene/environment interaction on the deleterious effect of obesity on cardiovascular risk factors.

Genetic variation of PLTP modulates lipoprotein profiles in hypoalphalipoproteinemia

Phospholipid transfer protein (PLTP) participates in key processes in lipoprotein metabolism, including interparticle phospholipid transfer, remodeling of HDL, cholesterol and phospholipid efflux from peripheral tissues, and the production of hepatic VLDL. The impact of PLTP on reverse cholesterol transport suggests that the gene may harbor sequence anomalies that contribute to disorders of HDL metabolism. The human PLTP gene was screened for sequence anomalies by DNA melting analysis in 276 subjects with hypoalphalipoproteinemia (HA) and 364 controls. The association with plasma lipid parameters was evaluated. We discovered 18 sequence variations, including four missense mutations and a novel polymorphism (c.-34G > C). In healthy controls, the c.-34G > C minor allele was associated with higher high density lipoprotein-cholesterol (HDL-C) and was depleted in subjects with HA. Linear regression models predict that possession of the rare allele decreases plasma triglyceride (TG) and TG/HDL-C and increases HDL-C independent of TG. Decreased PLTP activity was observed in one (p.R235W) of four (p.E72G, p.S119A, p.S124Y, and p.R235W) mutations in an in vitro activity assay. These findings indicate that PLTP gene variation is an important determinant of plasma lipoproteins and affects disorders of HDL metabolism.

Visceral fat thickness determined using ultrasonography is associated with anthropometric and clinical parameters of metabolic syndrome

The aim of this study is to find out the relation between the ultrasonographic (USG) measurements of the abdominal fat thickness and cardiovascular risk factors in metabolic syndrome. The thickness of subcutaneous fat (SF), visceral fat (VF) and preperitoneal fat (PF) was measured using USG in 75 subjects (35 women and 40 men) with metabolic syndrome. The body mass index (BMI), waist circumference (WC), systolic (SBP) and diastolic (DBP) blood pressures, fasting plasma glucose, fasting insulin and lipid parameters of all participants were recorded. Insulin resistance was estimated using HOMA-IR formula. BMI (p < 0.05), WC (p < 0.01), SBP (p < 0.001), DBP (p < 0.05), fasting insulin (p < 0.05), total cholesterol (p < 0.001) and triglyceride (p < 0.001) levels were found in correlation with VF thickness in the female group. There was a positive association between WC and SF thickness (p < 0.05) in the same group. In the male patients, BMI (p < 0.001), WC (p < 0.01), SBP (p < 0.05), DBP (p < 0.05) and triglyceride level (p = 0.01) were significantly correlated with VF thickness. SF thickness was associated with BMI (p < 0.001) and WC (p < 0.01) in this group. There was no relation between PF thickness and clinical variables in both groups (p > 0.05). It can be concluded that VF thickness may have a significant pathophysiological role in the development of the metabolic syndrome.

Diet, blood lipid profile and physical activity patterns in primary school children from a semi‐rural area of Greece

Risk factors for heart disease are becoming increasingly prevalent among young populations. The aim of this study was to assess the cardiovascular risk profile of young adolescents living in a semi-rural area of mainland Greece, Volos. A total of 198 children (106 females and 92 males) aged 11.6 +/- 0.4 years were randomly recruited. Mean body mass index was 20.4 +/- 3.5 kg m(-2), while 30.3% of children were overweight and 6.7% were obese; no differences were observed between boys and girls. Mean plasma cholesterol (4.93 +/- 0.75 mmol L(-1)), low-density lipoprotein-cholesterol (3.29 +/- 0.64 mmol L(-1)) and triglyceride (0.97 +/- 0.31 mmol L(-1)) concentrations were above age-specific recommended values. On the other hand, mean high-density lipoprotein-cholesterol was acceptable for 92.3% of the children. Self-reported daily energy intake (8.37 +/- 3.06 MJ) was adequate for age, but intake of fat was high (42.0 +/- 9.2% of energy) and that of carbohydrate was relatively low (44.5 +/- 10.0% of energy). Saturated fat consumption was elevated (15.6 +/- 4.3% of energy), while polyunsaturated fat intake fell short (4.8 +/- 1.6% of energy). The study participants spent 9.60 +/- 6.44 h week(-1) on moderate to vigorous physical activities, while they devoted 16.60 +/- 8.81 h week(-1) to sedentary activities. Boys spent significantly more time than girls on both physical (P < 0.001) and sedentary (P = 0.001) activities. No major gender differences were observed in anthropometric, dietary and plasma lipid parameters. The findings from the present study support the worrisome trends that have been documented in Greek youngsters elsewhere, and predict an unfavourable cardiovascular risk profile for the Greek population in the foreseeable future.

Effect of Japanese radish (Raphanus sativus) sprout (Kaiware-daikon) on carbohydrate and lipid metabolisms in normal and streptozotocin-induced diabetic rats

No information is available about the effects of Japanese radish sprout (JRS) on diabetes. To clarify the effects, the influence of JRS on carbohydrate and lipid metabolisms was investigated in normal and streptozotocin-induced diabetic rats. The rats were fed a diet containing 0%, 2.5% or 5% of JRS ad libitum for 21 days. Compared with the corresponding control groups, the JRS-fed normal rats showed lower plasma levels of total cholesterol (TC), triglycerides (TG), phospholipids (PL), fructosamine, glucose and insulin and higher plasma levels of low-density lipoprotein-cholesterol, whereas the JRS-fed diabetic rats showed lower plasma levels of fructosamine, glucose and insulin without changes in the plasma lipid parameters. JRS also decreased the hepatic TC, TG and PL levels in the normal rats and the TG level in the diabetic rats. These results showed that JRS had a hypoglycemic activity in both the normal and diabetic rats and partly improved lipid metabolism in the normal rats. JRS has the potential to alleviate hyperglycemia in cases where diabetes is present and to serve in the primary prevention of diabetes mellitus.

Intradialytic parenteral nutrition: comparison of olive oil versus soybean oilbasedlipid emulsions

Lipid, oxidative and inflammatory parameters are frequently altered in dialysis patients and may be worsened by intravenous lipid emulsions (ILE). We assessed the efficacy and tolerance of olive as compared with standard soybean oil-based ILE during intradialytic parenteral nutrition (IDPN). IDPN mixtures containing amino acids, glucose, and either olive oil (OO group, n 17) or soybean oil-based ILE (SO group, n 18) were administered in a 5-week randomized, double-blind study. On days 0 and 35, patients' nutritional status was assessed by BMI, normalized protein catabolic rate, predialytic creatinine, serum albumin and transthyretin; lipid metabolism by plasma LDL- and HDL-cholesterol, triacylglycerols, phospholipids, apo A-I, A-II, B, C-II, C-III, E and lipoprotein (a); oxidative status by alpha-tocopherol, retinol, selenium, glutathione peroxidase, malondialdehyde and advanced oxidized protein products; inflammatory status by serum C-reactive protein, orosomucoid, IL-2 and IL-6. No serious adverse event was observed. Significant changes were observed from day 0 to day 35 (P<0.05): nutritional criteria improved (albumin in OO; albumin, transthyretin and creatinine in SO); LDL-cholesterol, apo B, C-II, C-III and apo A-I/A-II ratio increased in both groups. HDL-cholesterol decreased in OO; apo E increased and lipoprotein (a) decreased in SO; alpha-tocopherol/cholesterol ratio increased in OO; malondialdehyde decreased in both groups; IL-2 increased in both groups. The between-group comparison only showed the following differences: alpha-tocopherol/cholesterol increased in OO; lipoprotein (a) decreased in SO. From these data, it was concluded that OO- and SO-based IDPNs similarly improved nutritional status and influenced plasma lipid, oxidative, inflammatory and immune parameters.

Th-P15:148 Lipid peroxidation in patients with retinal artery arteriosclerosis

Resveratrol is a major constituent of traditional Asian medicinal herbs and red wine and is suggested to be a potential antiatherosclerotic drug due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate whether resveratrol protects against atherosclerosis development in APOE*3-Leiden.CETP (E3L.CETP) mice and adds to the antiatherogenic effect of mild statin treatment, currently the most widely used antiatherogenic therapy. E3L.CETP mice were fed a cholesterol-rich diet without (control) or with resveratrol (0.01% w/w), atorvastatin (0.0027% w/w) or both for 14 weeks. During the study plasma lipid, inflammatory and oxidative stress parameters were determined. Resveratrol reduced atherosclerotic lesion area (−52%) in the aortic root, comparable to atorvastatin (−40%) and the combination of both drugs (−47%). The collagen/macrophage ratio in the atherosclerotic lesion, a marker of plaque stability, was increased by resveratrol (+108%), atorvastatin (+124%) and the combination (+154%). Resveratrol decreased plasma cholesterol levels (−19%) comparable to atorvastatin (−19%) and the combination (−22%), which was completely confined to (very)low-density lipoprotein cholesterol levels in all groups. Post hoc analyses showed that the antiatherogenic effect of atorvastatin could be explained by cholesterol lowering, while the antiatherosclerotic effect of resveratrol could be attributed to factors additional to cholesterol lowering. Markers of inflammation and oxidative stress were not different, but resveratrol improved macrophage function. We conclude that resveratrol potently reduces atherosclerosis development and induces a more stable lesion phenotype in E3L.CETP mice. However, under the experimental conditions tested, resveratrol does not add to the antiatherogenic effect of atorvastatin.

Quantitative trait loci in ABCA1 modify cerebrospinal fluid amyloid-β1-42 and plasma apolipoprotein levels

The ATP-binding cassette transporter A1 encoded by ABCA1 plays an integral role in the efflux of cellular cholesterol and phospholipids, but may also be a central mediator of beta-amyloid (Abeta) processing. Here, genetic association of the common R219K variant of ABCA1 is shown with cerebrospinal fluid (CSF) Abeta 1-42 levels, reinforcing emerging evidence of a connection between lipid and Abeta metabolism. In support of this finding we demonstrate for the first time that CSF cholesterol and Abeta 1-42 are correlated. To affirm the plausible impact of ABCA1 variation on cholesterol and related traits as well as to empower a survey of possible interactions (e.g. age, gender, and smoking), a large Swedish population consisting of over 2,700 individuals was enlisted and extensive measures of plasma lipid parameters carried out. These analyses revealed that R219K has a strong effect on apolipoprotein B (APOB) and LDL-cholesterol (LDL-C) among smokers (P = 0.000055 and P = 0.00059, respectively), but not among non-smokers. In contrast, no effect was evident with apolipoprotein A (APOA1) or HDL-cholesterol (HDL-C) levels. Plasma APOB and LDL-C, but not APOA1 and HDL-C, were shown to be markedly elevated in smokers versus non-smokers, affirming that smoking may selectively impact the former pathway. No other genetic markers in ABCA1 exhibit effects as large as R219K, although a modest independent effect of R1587K was observed. Our data illuminate a possible genetic link between Abeta and cholesterol metabolism, but also provide an intriguing example of an environmental exposure that may modify a genotype-phenotype relationship.

Relationships among acylation stimulating protein, adiponectin and complement C3 in lean vs obese type 2 diabetes

The purpose of this study was to determine the relationships between adipocyte hormones acylation stimulating protein (ASP), adiponectin, complement C3 (C3) (ASP precursor) and insulin, C-reactive protein (CRP), lipid profiles and insulin resistance in lean vs obese type 2 diabetes subjects. Lean type 2 diabetes subjects (DL n = 27) vs obese type 2 diabetes subjects (DO n = 55) were compared to age-matched nondiabetic groups (Obese, OB n = 55 and control, CTL n = 50). The DO group demonstrated significant increases in plasma ASP and C3 with decreases in plasma adiponectin as compared to CTL. Interestingly, these increases in ASP and C3 were as high, or greater, in the DL group in spite of normal weight. By contrast adiponectin in the DL group was comparable to CTL, in spite of marked insulin resistance. C3 correlated with insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR); ASP correlated with body mass index (BMI), glucose, insulin and plasma lipid parameters (non-esterified fatty acids (NEFA), triglyceride, cholesterol and apolipoprotein B). Adiponectin correlated with BMI, glucose, NEFA, triglyceride, high-density lipoprotein cholesterol and apolipoprotein A1 but not HOMA-IR, ASP or C3. CRP correlated only with HOMA-IR. Increased ASP and C3 are both associated with diabetes and related lipid factors but are not regulated coordinately. Adiponectin appears to be more closely related to body size (decreased in obese subjects) than insulin resistance in these subjects.

Plasma levels of the anti-inflammatory cytokine IL-10 and inflammatory cytokine IL-6 in patients with unstable angina

The plasma levels of inflammatory cytokine interleukin-6 (IL-6) and anti-inflammatory cytokine interleukin-10 (IL-10) in the patients with unstable angina or stable angina were determined and compared. In 30 patients with unstable angina and 22 patients with stable angina, plasma levels of IL-10 and IL-6 were detected by ELISA and plasma lipid parameters by lipid research clinical methods respectively. The results showed plasma levels of IL-10 were significantly lower in unstable angina group than in stable angina group (P = 0.005), while those of IL-6 were significantly increased in unstable angina group as compared with those in stable angina group (P = 0.039). There was a significantly negative correlation between IL-10 and IL-6 in patients with unstable angina (r = -0.41, P = 0.003). In the unstable angina group, IL-6 levels were obviously positively correlated with TC (r = 0.314, P = 0.023), but not with TG and HDL. There were no significant correlations between IL-10 and plasma lipid parameters. It was suggested that the decreased IL-10 and increased IL-6 might be associated with the atheromatous plaque stability and progression of coronary heart diseases. IL-10 may play an important role in preventing coronary vascular lesions.