Lipids in Health and Disease - Latest Articles

Plasma levels of lipometabolism-related miR-122 and miR-370 are increased in patients with hyperlipidemia and associated with coronary artery disease

Wei Gao — 2012-05-15T00:00:00Z

Background: Hyperlipidemia plays a crucial role in the development and progression of coronary artery disease (CAD). Recent studies have identified that microRNAs (miRNAs) are important regulators of lipid metabolism, but little is known about the circulating levels of lipometabolism-related miRNAs and their relationship with the presence of CAD in patients with hyperlipidemia. Methods: In the present study, we enrolled a total of 255 hyperlipidemia patients with or without CAD and 100 controls with normal blood lipids. The plasma levels of four known lipometabolism-related miRNAs, miR-122, miR-370, miR-33a, and miR-33b were quantified by real-time quantitative PCR. Blood levels of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol were determined. Furthermore, the severity of CAD was assessed with the Gensini score system based on the degree of luminal narrowing and its geographic importance. Results: Our results revealed for the first time that plasma levels of miR-122 and miR-370 were significantly increased in hyperlipidemia patients compared with controls, and the levels of miR-122 and miR-370 were positively correlated with TC, TG, and LDL-C levels in both hyperlipidemia patients and controls. Multiple logistic regression analysis demonstrated that the increased levels of miR-122 and miR-370 were associated with CAD presence, even after adjustment for other cardiovascular risk factors. Furthermore, miR-122 and miR-370 levels were positively correlated with the severity of CAD quantified by the Gensini score. However, both miR-33a and miR-33b were undetectable in plasma. Conclusions: Our results suggest that increased plasma levels of miR-122 and miR-370 might be associated with the presence as well as the severity of CAD in hyperlipidemia patients.

High-density lipoprotein subclass and particle size in coronary heart disease patients with or without diabetes

Li Tian — 2012-05-15T00:00:00Z

Background: A higher prevalence of coronary heart disease (CHD) in people with diabetes. We investigated the high-density lipoprotein (HDL) subclass profiles and alterations of particle size in CHD patients with diabetes or without diabetes. Methods: Plasma HDL subclasses were quantified in CHD by 1-dimensional gel electrophoresis coupled with immunodetection. Results: Although the particle size of HDL tend to small, the mean levels of low density lipoprotein cholesterol(LDL-C) and total cholesterol (TC) have achieved normal or desirable for CHD patients with or without diabetes who administered statins therapy. Fasting plasma glucose (FPG), triglyceride (TG), TC, LDL-C concentrations, and HDL3 (HDL3b and 3a) contents along with Gensini Score were significantly higher; but those of HDL-C, HDL2b+prebeta2, and HDL2a were significantly lower in CHD patients with diabetes versus CHD patients without diabetes; The prebeta1-HDL contents did not differ significantly between these groups. Multivariate regression analysis revealed that Gensini Score was significantly and independently predicted by HDL2a, and HDL2b+prebeta2. Conclusions: The abnormality of HDL subpopulations distribution and particle size may contribute to CHD risk in diabetes patients. The HDL subclasses distribution may help in severity of coronary artery and risk stratification, especially in CHD patients with therapeutic LDL, TG and HDL levels.

Long term stability of paraoxonase-1 and high-density lipoprotein in human serum

Piet Beekhof — 2012-05-14T00:00:00Z

Background: Paraoxonase-1 (PON1) is an enzyme with numerous functions and receives an increasing interest in clinical and epidemiological studies. Sometimes samples are stored for longer periods at a certain temperature. Therefore the stability of PON1 activity must be checked and retained upon storage for longer periods. Results: In this study the stability of PON1 activity has been tested in human serum samples during storage up to 12 months at 3 commonly used temperatures, -20degreesC, -70degreesC and 196degreesC. It was found that the stability of the PON1 activity is constant during 12 months of storage at 70degreesC and 196degreesC. Storage at 20degreesC resulted in a small but statistically significant decrease after 6 months to about 94% of its original value. Nonetheless, the rank order between the samples at T = 0 and 12 months remained the same. The same temperature dependence was found for the associated high-density lipoprotein. Conclusions: It can be concluded that 70degreesC is the right temperature for storage to maintain the PON1 activity for at least one year. Storage at a lower temperature in liquid nitrogen (196degreesC) is not necessary.

Supplementation of highly concentrated beta-cryptoxanthin in a satsuma mandarin beverage improves adipocytokine profiles in obese Japanese women

Masako Iwamoto — 2012-05-14T00:00:00Z

Background: Serum beta-cryptoxanthin levels are lower in overweight subjects than in normal subjects. Abnormalities of adipocytokine profiles in obesity subjects have been reported. There are several reports that serum beta-cryptoxanthin levels in them were relatively lower than normal subjects.ObjectiveWe hypothesize that supplementation of highly concentrated beta-cryptoxanthin improves serum adipocytokine profiles in obese subjects. This study tested the association between beta-cryptoxanthin intake and serum adipocytokine levels. Methods: An intervention study consisted of a 3-week long before-and-after controlled trial, where beta-cryptoxanthin (4.7 mg/day) was given to 17 moderately obese postmenopausal women. Results: The results indicated no significant changes in body weight or body mass index (BMI). Serum beta-cryptoxanthin levels increased significantly by 4-fold. Serum high molecular weight (HMW)-adiponectin levels increased significantly, while serum plasminogen activator inhibitor (PAI)-1 levels decreased. Conclusions: We concluded that increasing the intake of beta-cryptoxanthin to approximately 4 mg per day for 3 weeks may have beneficial effects on the serum adipocytokine status and consequently alleviate progression of metabolic syndrome.

Oleamide activates peroxisome proliferator-activated receptor gamma (PPARgamma) in vitro

Mauro Dionisi — 2012-05-14T00:00:00Z

Background: Oleamide (ODA) is a fatty acid primary amide first identified in the cerebrospinal fluid of sleep-deprived cats, which exerts effects on vascular and neuronal tissues, with a variety of molecular targets including cannabinoid receptors and gap junctions. It has recently been reported to exert a hypolipidemic effect in hamsters. Here, we have investigated the nuclear receptor family of peroxisome proliferator-activated receptors (PPARs) as potential targets for ODA action. Results: Activation of PPARalpha, PPARbeta and PPARgamma was assessed using recombinant expression in Chinese hamster ovary cells with a luciferase reporter gene assay. Direct binding of ODA to the ligand binding domain of each of the three PPARs was monitored in a cell-free fluorescent ligand competition assay. A well-established assay of PPARgamma activity, the differentiation of 3T3-L1 murine fibroblasts into adipocytes, was assessed using an Oil Red O uptake-based assay. ODA, at 10 and 50 muM, was able to transactivate PPARalpha, PPARbeta and PPARgamma receptors. ODA bound to the ligand binding domain of all three PPARs, although complete displacement of fluorescent ligand was only evident for PPARgamma, at which an IC50 value of 38 muM was estimated. In 3T3-L1 cells, ODA, at 10 and 20 muM, induced adipogenesis in an apparently concentration-dependent manner. Conclusions: We have, therefore, identified a novel site of action of ODA through PPAR nuclear receptors and shown how ODA should be considered as a weak PPARgamma ligand in vitro.

Association of rs5888 SNP in the scavenger receptor class B type 1 gene and serum lipid levels

Dong-Feng Wu — 2012-05-14T00:00:00Z

Background: Bai Ku Yao is a special subgroup of the Yao minority in China. The present study was undertaken to detect the association of rs5888 single nucleotide polymorphism (SNP) in the scavenger receptor class B type 1 (SCARB1) gene and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods: A total of 598 subjects of Bai Ku Yao and 585 subjects of Han Chinese were randomly selected from our stratified randomized cluster samples. Genotypes of the SCARB1 rs5888 SNP were determined by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results: The levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI were lower but ApoB was higher in Bai Ku Yao than in Han (P < 0.05-0.001). The frequencies of C and T alleles were 78.3 % and 21.7 % in Bai Ku Yao, and 73.7 % and 26.3 % in Han (P < 0.01); respectively. The frequencies of CC, CT and TT genotypes were 60.0 %, 36.6 % and 3.4 % in Bai Ku Yao, and 54.2 %, 39.0 % and 6.8 % in Han (P < 0.01); respectively. The subjects with TT genotype in both ethnic groups had lower HDL-C and ApoAI levels than the subjects with CC or CT genotype (P < 0.05 for all). Subgroup analyses showed that the subjects with TT genotype in Bai Ku Yao had lower HDL-C and ApoAI levels in males than the subjects with CC or CT genotype (P < 0.05 for all), and the T allele carriers had higher TC, LDL-C and ApoB levels in females than the T allele noncarriers (P < 0.05 for all). The participants with TT genotype in Han also had a lower tendency of HDL-C and ApoAI levels in males than the participants with CC or CT genotype, but the difference did not reach statistically significant (P = 0.063 and P = 0.086; respectively). The association of serum HDL-C and ApoAI levels and genotypes was confirmed by the multiple linear regression analysis in both ethnic groups. Serum lipid parameters were also correlated with several environmental factors. Conclusions: The differences in serum lipid levels between the two ethnic groups might partially attribute to the differences in the SCARB1 rs5888 SNP and several environmental factors.

Minor lipid components of some Acacia species: potential dietary health benefits of the unexploited seeds

Nizar Nasri — 2012-05-11T00:00:00Z

Background: Oilseed samples from four Acacia species (A. cyclops, A. ligulata, A. salicina and A. cyanophylla) were analyzed in order to evaluate the potential nutritional value of their unexploited seeds. Methods: Samples were collected from different Tunisian geographic locations. Seed oils were extracted and carotenoids, tocopherols and sterols were analyzed using chromatographic methods. Results: The studied Acacia seeds seem to be quite rich in lipids (from 6% to 12%). All Acacia species contains mainly the xanthophylls zeaxanthin and lutein compounds: from ca. 38 mg.kg-1 of total lipids (A. cyclops) to ca 113 mg.kg-1 of total lipids (A. cyanophylla). Total tocopherols varied from ca. 221 mg.kg-1 of total lipids (A. cyclops) to ca. 808 mg.kg-1 of total lipids (A. ligulata). Sterols are highly present and their contents ranged between ca. 7 g. kg-1 of total lipids (A. salicina) and 11 g. kg-1 of total lipids (A. cyclops). Conclusion: This study highlights that these unexploited seeds might have a potential nutritional value and encourages researchers to more explore and find developments for these plants for healthy purposes.

Dietary sea cucumber cerebroside alleviates orotic acid-induced excess hepatic adipopexis in rats

Bei Zhang — 2012-05-08T00:00:00Z

Background: Nonalcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease in industrialized countries. The present study was undertaken to explore the preventive effect of dietary sea cucumber cerebroside (SCC) extracted from Acaudina molpadioides in fatty liver rats. Methods: Male Wistar rats were randomly divided into four groups including normal control group, NAFLD model group, and two SCC-treated groups with SCC at 0.006% and 0.03% respectively. The fatty liver model was established by administration of 1% orotic acid (OA) to the rats. After 10d, serum and hepatic lipid levels were detected. And the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were also determined. Besides, to gain the potential mechanism, the changes of key enzymes and gene expressions related to the hepatic lipid metabolism were measured. Results: Dietary SCC at the level of 0.006% and 0.03% ameliorated the hepatic lipid accumulation in fatty liver rats. SCC administration elevated the serum triglyceride (TG) level and the ALT, AST activities in OA-fed rats. The activities of hepatic lipogenic enzymes including fatty acid synthase (FAS), malic enzyme (ME) and glucose-6-phosphatedehydrogenase (G6PDH) were inhibited by SCC treatment. And the gene expressions of FAS, ME, G6PDH and sterol-regulatory element binding protein (SREBP-1c) were also reduced in rats fed SCC. However, dietary SCC didn't affect the activity and mRNA expression of carnitine palmitoyltransferase (CPT) in liver. Besides, suppression of microsomal triglyceride transfer protein (MTP) activity was observed in SCC-feeding rats. Conclusions: These results suggested that dietary SCC could attenuate hepatic steatosis due to its inhibition of hepatic lipogenic gene expression and enzyme activity and the enhancement of TG secretion from liver.

Treatment of chronic hemodialysis patients with low-dose fenofibrate effectively reduces plasma lipids and affects plasma redox status

Agnieszka Makowka — 2012-05-07T00:00:00Z

Dyslipidemia is common in chronic hemodialysis patients and its underlying mechanism is complex. Hemodialysis causes an imbalance between antioxidants and production of reactive oxygen species, which induces the oxidative stress and thereby may lead to accelerated atherosclerosis. Statins have been found to be little effective in end-stage kidney disease and other lipid-lowering therapies have been only scarcely studied. The study aimed to assess the effect of low-dose fenofibrate therapy on plasma lipids and redox status in long-term hemodialysis patients with mild hypertriglyceridemia.Twenty seven chronic hemodialysis patients without any lipid-lowering therapy were included in a double-blind crossover, placebo-controlled study. The patients were randomized into two groups and were given a sequence of either 100 mg of fenofibrate per each hemodialysis day for 4 weeks or placebo with a week-long wash-out period between treatment periods. Plasma lipids, high sensitive C-reactive protein (CRP), urea, creatinine, electrolytes, phosphocreatine kinase (CK), GOT, GPT and plasma thiols (total and free glutathione, homocysteine, cysteine and cysteinylglycine) were measured at baseline and after each of the study periods. Plasma aminothiols were measured by reversed phase HPLC with thiol derivatization with 2-chloro-1-methylquinolinium tetrafluoroborate.Fenofibrate therapy caused a significant decrease of total serum cholesterol, LDL cholesterol and triglycerides and an increase of HDL cholesterol. The treatment was well tolerated with no side-effects but there was a small but significant increase of CK not exceeding the upper limit of normal range. There were no changes of serum CRP, potassium, urea, and creatinine and liver enzymes during the treatment. Neither total nor total free cysteinylglycine and cysteine changed during the study but both total and free glutathione increased during the therapy with fenofibrate and the same was observed in case of plasma homocysteine.The study shows that a treatment with reduced fenofibrate dose is safe and effective in reducing serum triglycerides and cholesterol in chronic dialysis patients and may shift plasma aminothiol balance towards a more antioxidative pattern.

Association of ATP binding cassette transporter G8 rs4148217 SNP and serum lipid levels in Mulao and Han nationalities

Qing Li — 2012-05-01T00:00:00Z

Background: The association of ATP binding cassette transporter G8 gene (ABCG8) rs4148217 single nucleotide polymorphism (SNP) and serum lipid profiles is still controversial in diverse racial/ethnic groups. Mulao nationality is an isolated minority in China. The aim of this study was to evaluate the association of ABCG8 rs4148217 SNP and several environmental factors with serum lipid levels in the Guangxi Mulao and Han populations. Methods: A total of 634 subjects of Mulao nationality and 717 participants of Han nationality were randomly selected from our previous samples. Genotyping of the ABCG8 rs4148217 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results: The genotypic and allelic frequencies of ABCG8 rs4148217 SNP were different between the two nationalities (P < 0.01 for each), the frequency of A allele was higher in Mulao than in Han. The A allele carriers in Han had lower high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo) A1 levels than the A allele noncarriers (P < 0.05 for each), whereas the A allele carriers in Mulao had lower ApoA1 levels than the A allele noncarriers (P < 0.05). Subgroup analyses showed that the A allele carriers in Han had lower HDL-C and higher triglyceride (TG) levels in females but not in males than the A allele noncarriers (P < 0.05 for each), and the A allele carriers in Mulao had lower ApoA1 levels in females but not in males than the A allele noncarriers (P < 0.05). The levels of TG and HDL-C in Han, and ApoA1 in Mulao were associated with genotypes in females but not in males (P < 0.05-0.01). Serum lipid parameters were also correlated with several environmental factors (P < 0.05-0.001). Conclusions: The ABCG8 rs4148217 SNP is associated with serum TG, HDL-C and ApoA1 levels in our study populations, but this association is different between the Mulao and Han populations. There is a sex (female)-specific association in both ethnic groups.