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Adiponectin has been reported to have antiatherogenic, antidiabetic properties and was proposed as an important mediator of insulin action and glucose metabolism. This study was conducted to determine weight loss effects on the plasma adiponectin levels and clinical parameters including oxidative DNA damage and C-reactive protein (CRP) in overweight-obese subjects. A total of 184 overweight-obese volunteers underwent a clinical intervention study consisting of −1255 kJ/d for 12 weeks. Anthropometic parameters, blood lipid profiles, glucose, insulin, CRP, and baseline DNA damage using comet assay and adiponectin concentrations were determined at baseline and at 12 weeks of intervention. The treatment induced modest weight loss averaged 4.75% of initial body weight. C-reactive protein ( P P P P P P In conclusion, modest weight loss improved metabolic parameters including blood lipids, insulin resistance, CRP, and DNA damage, but did not increase plasma levels of adiponectin in overweight-obese subjects. However, the increases in plasma adiponectin after 12 weeks were observed in the subjects with a higher degree of weight loss.

Limited data are available on the association of insulin resistance, adipokines, and in vivo lipid peroxidation. We investigated the relationships between insulin resistance, adipokines (leptin, adiponectin, and resistin), and oxidative stress in nondiabetic, hypercholesterolemic patients. Seventy-six nondiabetic patients with hypercholesterolemia participated in this cross-sectional study. Fasting glucose and insulin concentrations were analyzed. Serum leptin, adiponectin, and resistin concentrations and urinary excretion of 8-epi-prostaglandin F(2alpha) (8-epi-PGF(2alpha)) were determined using enzyme-linked immunosorbent assay. We divided all subjects into 3 groups, classified by the tertiles of homeostasis model assessment of insulin resistance (HOMA-IR) values, and clinical parameter comparisons were made among the 3 groups. The results showed that serum leptin (P < .001) and adiponectin levels (P < .05) were significantly different among the groups, although serum resistin was not different. Furthermore, the group with the highest HOMA-IR had a significantly higher urinary 8-epi-PGF(2alpha) excretion than the group with the lowest HOMA-IR (P = .017). Circulating leptin was positively correlated with urinary 8-epi-PGF(2alpha) (r = 0.323, P < .01) and HOMA-IR (r = 0.524, P < .001). Circulating adiponectin was negatively correlated with body mass index (r = -0.252, P < .05) and HOMA-IR (r = -0.228, P < .05). We could not find a relationship between circulating adiponectin or resistin and urinary 8-epi-PGF(2alpha) excretion. Stepwise multiple linear regression analysis showed that leptin was associated with the urinary 8-epi-PGF(2alpha) excretion after adjusting for age, sex, body mass index, blood lipids, and HOMA-IR (P = .002). In conclusion, our results show that more insulin-resistant state of nondiabetic, hypercholesterolemic patients is associated with decreased adiponectin and increased leptin and urinary 8-epi-PGF(2alpha) levels, although no relationship with resistin was observed. Furthermore, serum leptin independently contributed to urinary 8-epi-PGF(2alpha) excretion.

The purpose of this study was to determine whether common single nucleotide polymorphisms (SNPs) at the adiponectin (ADIPOQ) locus influence changes in circulating adiponectin and the features of insulin resistance in response to a weight loss intervention.In total, 294 nondiabetic/overweight-obese Koreans participated in a clinical intervention study lasting 12 weeks involving a caloric reduction of -300kcal/day.Plasma adiponectin, blood lipids, glucose and insulin concentrations were measured at baseline and after weight loss. Insulin resistance was estimated by homeostasis model assessment insulin resistance (HOMA-IR) derived from fasting glucose and insulin concentrations. We genotyped for three SNPs, 45TG, 276GT and -11377CG.At baseline, HOMA-IR was significantly higher in GG homozygotes than in carriers of the T allele at SNP276GT of the adiponectin gene (P0.05). With regard to SNP45TG and SNP -11377CG, we did not find any genotype related differences in baseline levels of HOMA-IR and adiponectin. In the 45/276 haplotype test, homozygous for the TG haplotype had significantly lower concentrations of plasma adiponectin (P0.05). After the 12-week weight loss intervention, the significant decreases in HOMA-IR (P0.001) and increases in adiponectin (P0.01) were observed in GG homozygotes at SNP276, which were not shown in carriers of the T allele. Furthermore, there was a significant difference in the decreases in HOMA-IR between the GG homozygotes and carriers of the T allele at SNP276 (P0.05). Regarding SNP45TG and SNP -11377CG, there was no association between SNP45TG and SNP -11377CG and decreases in HOMA-IR. In the 45/276 haplotype test, there was a significant difference in changes of adiponectin levels among those with different haplotype combinations (P0.05).The SNP276GT of the ADIPOQ gene is associated with different responses of circulating adiponectin and insulin resistance to mild weight loss in overweight-obese subjects.

The hypertrophy of vascular smooth muscle cells (VSMCs) is critical in vascular remodeling associated with hypertension, atherosclerosis, and restenosis. Recently, leptin has appeared to play a pivotal role in vascular remodeling. However, the mechanism by which leptin induces hypertrophy in vascular smooth muscle cells is still unknown. We studied the role of leptin as a potential hypertrophic factor in rat VSMCs. In the present study, leptin significantly increased [(3)H]leucine incorporation and the total protein/DNA ratio in VSMCs. The maximal hypertrophic effect was at 100ng/ml of leptin. Leptin induced phosphorylation and activation of p38 mitogen-activated protein (p38 MAP) kinase and of signal transducers and activators of transcription 3 in a concentration- and time-dependent manner. A p38 MAP kinase inhibitor SB203580 significantly inhibited leptin-induced hypertrophy, AG490 (a JAK2 inhibitor) partially inhibited it, and other MAP kinase inhibitors, PD98059 (an ERK inhibitor) and SP600125 (a JNK inhibitor), had no effect. These results indicate that leptin directly stimulates cellular hypertrophy via p38 MAP kinase in rat VSMCs.

Background: The objective of this study was to evaluate the effects of micellar phytosterols on cholesterol absorption in humans. Methods: 24 healthy adults (mean age 37 years, 16 women and 8 men) underwent four cholesterol-absorption tests to compare the effects of micellar phytosterols supplement containing 500, 300, 200 mg phytosterols and placebo on cholesterol absorption in a cross-over design. Individual absorption tests were separated by 2 weeks. Using the single oral isotope method, inhibition of cholesterol absorption was determined by gas-chromatography mass spectrometry measurement of the differences in plasma hexadeuterated cholesterol enrichment 4 days after test meals with or without phytosterols. Each test meal provided 500 kcal and 89 mg cholesterol including 40 mg tracer cholesterol. We used a general linear mixed model with SAS to test the significance of treatment effect. Results: Micellar phytosterols had a significant overall effect on cholesterol absorption (p = 0.0002), reduced cholesterol absorption by 23.3% at a dose of 300 mg phytosterols (p = 0.0004) and by 32.0% at a dose of 500 mg phytosterols (p = 0.0001) compared with the placebo. The effect of 200 mg treatment did not reach statistical significance but there was a tendency (p = 0.052). Conclusion: Water-dispersible, micellar phytosterols reduced cholesterol absorption effectively at very low doses.

We investigated whether apo E polymorphism contributes to the variations in blood lipid profile, apolipoprotein B and small dense LDL in 92 clinically healthy Korean subjects who traditionally consume a low fat and low cholesterol diet (40 males, 52 females, aged 24-60). Body weight, height, waist and hip circumference were measured. Body mass index (BMI) and waist to hip ratio (WHR) were calculated. Dietary intake was assessed by using a semi-quantitative Food Frequency Questionnaire. Alleles ϵ3, ϵ2 and ϵ4 showed relative frequencies of 72.8%, 7.6%, and 19.6%, respectively, in the subjects. In order to estimate the independent effects of alleles ϵ2 and ϵ4, as compared with ϵ3 homozygosity, on lipid and apolipoprotein parameters, multiple linear regression was performed after adjustment for confounding variables such as age, gender, BMI, WHR, smoking and alcohol consumption. Apo E polymorphism was associated with variations in the serum concentrations of LDL-cholesterol, apolipoprotein B and concentration of LDLIII (d 1.044 – 1.063 g/ml), and was higher in the allele ϵ4 than ϵ3 homozygosity. Moreover, the allele ϵ4 significantly increased the concentration of LDLIII even after adjustment for the serum concentration of triacylglycerol. The allele ϵ2 did not show any significant effects on lipid or apolipoprotein concentrations. Our results showed that the apo E4 isoform was related to higher levels of LDL-cholesterol and small dense LDL in Koreans who are exposed to a low fat, carbohydrate rich diet.

We investigated the effect of a beverage containing plant sterols on serum concentrations of triacylglycerol and cholesterol of hypercholesterolemic subjects that consume a low cholesterol diet. Fifty three hypercholesterolemic subjects (fasting LDL-cholesterol > 130 mg/dl) were fed a placebo beverage for 4 weeks followed by feeding a test beverage containing plant sterols for 8 weeks in a single-blind, randomized cross-over study. The subjects were instructed to maintain the same amount of dietary intake of fat and cholesterol during the study. After 4 weeks of treatment with a beverage containing of 1.6 g/d of plant sterols, subjects whose concentrations of LDL-cholesterol did not decrease by 15% received 3.2 g/d of plant sterols. The total study population who completed the whole protocol was 45 subjects (15 males, 30 females, average age 56). At baseline, the average dietary daily intakes of saturated fat and cholesterol were relatively low with 11.12 g and 135.2 mg, respectively. After 8 week treatment with plant sterols, serum concentrations of total cholesterol and LDL-cholesterol were decreased significantly by 4.38% (p < 0.05), 8.28% (p < 0.05) respectively. However, concentrations of HDL-cholesterol and triacylglycerol did not change significantly. We conclude that a beverage containing plant sterols decrease serum total cholesterol and LDL-cholesterol concentrations significantly in subjects with relatively low dietary cholesterol intake.

Objectives We examined whether arginase inhibition influences hepatic metabolic pathways and whole body adiposity in diet-induced obesity. Methods and Results After obesity induction by a high fat diet (HFD), mice were fed either the HFD or the HFD with an arginase inhibitor, Nω-hydroxy-nor-L-arginine (nor-NOHA). Nor-NOHA significantly prevented HFD-induced increases in body, liver, and visceral fat tissue weight, and ameliorated abnormal lipid profiles. Furthermore, nor-NOHA treatment reduced lipid accumulation in oleic acid-induced hepatic steatosis in vitro. Arginase inhibition increased hepatic nitric oxide (NO) in HFD-fed mice and HepG2 cells, and reversed the elevated mRNA expression of hepatic genes in lipid metabolism. Expression of phosphorylated 5′ AMPK-activated protein kinase α was increased by arginase inhibition in the mouse livers and HepG2 cells. Conclusions Arginase inhibition ameliorated obesity-induced hepatic lipid abnormalities and whole body adiposity, possibly as a result of increased hepatic NO production and subsequent activation of metabolic pathways involved in hepatic triglyceride metabolism and mitochondrial function.

It is generally accepted that diet modification provides beneficial effects on the management of diabetes. In the present study, we evaluated the effects of diet modification on nutrient intake and quality of life in a large sample of diabetic patients. This study was conducted using data from the Korea National Health and Nutrition Examination Survey IV and V (2007-2010). A total of 2,484 of diabetic patients were included in the analysis. Then, we compared the overall quality of dietary intake between diabetic patients with diet modification and those without dietary modification. The result showed that subjects on diabetic diet (DDG) showed lower levels of total cholesterol, triglyceride, and AST before and after the adjustment for covariates (all p < 0.05). The results of nutrient assessment showed that DDG had lower intakes of total energy, fat, and carbohydrate (all p < 0.05), but higher intakes of energy from protein, vitamin B1, vitamin B2, niacin and vitamin C than NDG. (all p < 0.05). In addition, nutritional adequacy ratio of calcium and vitamin B2 were significantly higher in DDG than those in normal diet group (NDG) (p < 0.05). However, we observed no significant differences in quality of life between two groups. In conclusion, diet modification in diabetic patients seemed to be effective to improve blood lipid profile and the adequacy of nutrient intake without sacrificing the quality of life.

The aims of this study were to examine the association between circulating vitamin D (25(OH) D) levels and depressive symptoms and to evaluate the associations between depressive symptoms and various sociodemographic factors. Data on serum 25(OH) D levels, sociodemographic factors, and information on depressive symptoms were obtained from the Korea National Health and Nutrition Examination Survey V-1 2010. A total of 3,570 Koreans aged >= 20 years were included in the statistical analysis. Subjects with depressive symptoms had lower serum levels of 25(OH) D (41.6 +/- 16.2 nmol/L) than those without (44.3 +/- 16.2 nmol/L; P-value= 50 nmol/L) revealed fewer depressive symptoms (OR, 0.72; 95% CI, 0.53-0.97; P-value = 0.032) after adjusting for multiple factors. In addition, females (OR, 3.61; 95% CI, 2.55-5.11; P-value, 0.001), problematic alcohol users (OR, 2.33; 95% CI, 1.63-3.34; P-value, 0.001), current smokers (OR, 1.43; 95% CI, 1.02-1.99; P-value = 0.036), and subjects who experienced weight loss (OR, 1.78; 95% CI, 1.30-2.44; P-value, 0.001) were more likely to answer "yes" on question for depressive symptoms. In conclusion, low serum levels of 25(OH) D were associated with an increased risk for depression symptoms in Korean adults. In addition, several sociodemographic factors were related to the depressive symptoms. Our results provide insight into the relationships among vitamin D status, sociodemographic factors, and depression in the Korean population.

The aim of this study was to determine whether 1-deoxynojirimycin (DNJ) isolated from Bacillus subtilis MORI beneficially influences lipid metabolism and mitochondrial function in the liver of mice fed a high-fat diet in addition to the anti-obesity properties of DNJ. Male C57BL/6 mice (n = 29; 5 weeks old) were randomly assigned to three groups: normal control diet (CTL, n = 10), high-fat diet (HF, n = 10), and high-fat diet supplemented with DNJ (DNJ, n = 9). After 12 weeks, the HF group exhibited higher overall weight gain, of the liver, and of various fat pads than the CTL and DNJ groups did. The HF group also showed greater expression of C/EBPα and CD36 mRNA in the liver than that in the CTL and/or DNJ groups. In addition, mRNA expressions of AAC and FAS were lower, while mRNA expression of PGC-1β was higher in the liver of the DNJ group than that of the HF group. The hepatic expression of p-AMPK/AMPK was higher in the DNJ group than in the HF group. This study provides novel insight into the protective effect of DNJ supplementation against obesity-induced hepatic lipid abnormalities and mitochondrial dysfunction.

In the present study, we evaluated the association between dietary patterns and pulmonary functions in Korean women older than 40 years. This study analyzed the data from the Korea National Health and Nutrition Examination Survey IV and V (2007–2010). In total, 7615 women were included in the analysis. Using principal component analysis, two dietary patterns were identified, namely a balanced diet pattern (vegetables, fish, meat, seaweed, and mushrooms) and a refined diet (snacks, bread, milk, dairy products, and fast food). The refined diet pattern was positively associated with energy from fat but negatively associated with vitamin A, β-carotene, niacin, and fiber. After adjusting for potential confounders, the refined diet pattern was negatively associated with levels of predicted forced vital capacity (odds ratio (OR): 0.84, 95% confidence intervals (CIs): 0.70, 0.99) and predicted forced expiratory volume in 1 second (OR: 0.79, 95% CIs: 0.66, 0.93). In conclusion, the refined diet pattern was associated with decreased pulmonary function in Korean women. This information may be useful toward the development of nutritional guidelines for improving pulmonary function in Korean women.

We grew one-dimensional GaN nanoneedles on AlN/Si(111) substrates at HCl/NH3 gas-flow ratios of 1/20, 1/30, and 1/50 using the hydride vapor-phase epitaxy (HVPE) method. Field emission-scanning electron microscopy (FE-SEM) images of GaN nanoneedles show that the vertical growth rate of GaN nanoneedles increases with increasing gas-flow ratio, but there is little growth in the lateral direction. X-ray diffraction patterns indicate that GaN nanoneedles grew with c-axes oriented perpendicular to the substrate. The room-temperature PL spectrum of GaN nanoneedles was detected at 3.237 eV of near-band-edge transitions.

We tested whether long-term administration of voglibose (VO) prevents diet induced obesity in addition to hypoglycemic effects in high fat fed mice and further investigated the underlying mechanisms by which voglibose exerts its weight lowering effect. Male C57BL/6 mice were fed ad libitum for 12 weeks with the control diet (CTL), high-fat diet (HFD) or the HFD with VO supplementations. Blood lipid profile, plasma leptin levels and hepatic triglyceride content, as well as expressions of genes involved in appetite and mitochondrial function were examined. The results showed that VO significantly reduced body weight, fat mass and energy intakes in high fat fed mice. VO showed improved metabolic profiles including blood glucose, triglyceride and free fatty acid. Elevated levels of plasma leptin in HFD were significantly reduced with the VO, furthermore, VO modulated the hypothalamic expressions of leptin receptors and appetite related genes. VO showed the upregulated expressions of PGC-1 in the liver and epididymal adipose tissue. In conclusion, VO may exert antiobesity properties through reductions in energy intake and improvement in mitochondrial function, indicating that VO has potential therapeutic use in patients with obesity, type 2 diabetes, and related complications.

We have demonstrated that 1-deoxynojirimycin (DNJ) isolated from Bacillus subtilis MORI could enhance the levels of adiponectin and its receptors in differentiated 3T3-L1 adipocytes, which has been shown to be effective in lowering blood glucose levels and enhancing insulin sensitivity. DNJ was not toxic to differentiated 3T3-L1 adipocytes for up to a concentration of 5 microM. In terms of expression levels of adiponectin and its receptors (AdipoR1 and AdipoR2), DNJ in concentrations as low as 0.5 microM elevated both mRNA and protein levels of adiponectin and transcript levels of AdipoR1 and AdipoR2. In addition, DNJ increased phosphorylation of 5' adenosine monophosphateactivated protein kinase (AMPK) in a statistically significant manner. Finally, treatment with DNJ resulted in increased mRNA expression of glucose transporter 4 (GLUT4), which encodes for a glucose transporter, along with a significant increase in glucose uptake into the adipocytes based on results of a 2-deoxy-D-[3H] glucose uptake assay. Our findings indicate that DNJ may greatly facilitate glucose uptake into adipose tissues by increasing the action of adiponectin via its up-regulated expression as well as its receptor genes. In addition, the glucose-lowering effects of DNJ may be achieved by an increased abundance of GLUT4 protein in the plasma membrane, as a consequence of the increased transcript levels of the GLUT4 gene and the activation of AMPK.

Objective We examined the association of cardiac hypertrophy or fibrosis with the phospholipid fatty acid (FA) composition of heart and kidney in hypertensive rats. Design and methods Eight-week-old spontaneously hypertensive rats (SHRs) (n = 8) and Wistar Kyoto rats (WKYs, n = 8) as a normotensive control, were fed ad libitum for 6 weeks with regular AIN-76 diet. Phospholipid FA compositions in the left ventricle and kidney were measured and histological analyses were performed. Results Compared with WKYs, SHRs had lower proportions of γ-linolenic acid , α-linolenic acid , eicosadienoic acid, eicosatrienoic acid , dihomo-γ-linoleic acid, docosadienoic acid and nervonic acid in heart, and stearic acid (SA), γ-linolenic acid, and eicosapentaenoic acid (EPA) in kidney. After adjusting for food intake, SHRs still maintained higher proportions of SA, and total saturated FAs in the heart and a lower proportion of eicosapentaenoic acid in the kidney. Additionally, compared with WKYs, SHRs showed larger cardiomyocyte diameters in the left ventricles, indicating cardiac hypertrophy and interstitial fibrosis . Cardiomyocyte diameters also positively correlated with cardiac SA (r = 0.550, p Conclusion Tissue FA compositions were associated with cardiac hypertrophy in a hypertensive setting, implicating the pathogenic role of tissue FAs in hypertension and related complications.

The aim of the present study was to examine the effect of quercetin-rich onion peel extract (OPE) on anti-differentiation in 3T3-L1 preadipocytes and the antiobesity in high-fat fed rats. We found that lipid accumulations and TG contents in 3T3-L1 cells were markedly suppressed by OPE. The mRNA levels of activating protein (AP2) were down-regulated and those of carnitine palmitoyl transferase-1 α (CPT-1α) and fatty acid binding protein 4 (FABP4) were up-regulated by 75 and 100 μg/ml OPE. Body weight, retroperitoneal and mesenteric fat weights of SD rats were significantly lower in the 8 week high fat (HF) diet+0.72% OPE group than in the HF group. Peroxisome proliferator-activated receptor (PPAR)γ mRNA levels were down-regulated in the epididymal fat of OPE than those of control and HF, and significant down-regulation of CCAAT/enhancer binding protein (C/EBP)α mRNA levels in OPE was also observed than the control. The mRNA levels of CPT-1α and uncoupling protein-1 (UCP-1) were up-regulated by the OPE, while those of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) were down-regulated in HF and OPE groups compared to control group. These results suggest that quercentin-enriched OPE may have antiobesity effects by suppressing preadipocyte differentiation and inhibiting adipogenesis.

Food insecurity is an ongoing public health issue and contributes to mental health status. We investigated whether food insecurity is associated with inadequate nutrient intake and whether it affects mental health indicators (perceived stress/experience of depressive symptom/suicidal ideation) and quality of life (QOL) among Koreans (n = 5862, 20–64 years) using data from the Korea National Health and Nutritional Examination Survey (2012–2013). Household food security status was categorized as “food-secure household”, “food-insecure household without hunger”, and “food-insecure household with hunger”. Data on food insecurity, sociodemographic factors, nutrient intake, mental health indicators, and QOL were used. A logistic regression model was conducted to determine odds ratios (ORs) for psychological health. A greater proportion of food-insecure participants were nutritionally deficient compared with expectations of the 2015 Korean Dietary Reference Intakes. These deficiencies were generally higher in both “food-insecure household” groups. Both “food-insecure household” groups, particularly the “food-insecure household with hunger” group showed significantly adverse mental health status (ORs: 1.52–3.83) and lower QOL (ORs: 1.49–3.92) than did the “food-secure household” group before and after adjusting for sex, age, education, household income, smoking/alcohol consumption, physical activity, marital status, and receiving food assistance. In conclusion, food insecurity may be significantly associated with adverse mental health indicators and decreased QOL in young/middle-aged Koreans.

We aimed to test whether fisetin could modulate cholesterol homeostasis in rats with diet-induced hypercholesterolemia, and further investigated the underlying mechanisms by which fisetin exerts its cholesterol lowering effect. Blood lipid profile, hepatic cholesterol content, as well as gene expressions in cholesterol metabolism were examined. Elevated levels of total cholesterol and LDL-cholesterol, along with hepatic cholesterol content in a high fat group were found to be significantly reduced by fisetin. The high fat diet significantly decreased hepatic mRNA levels of LDLR, SREBP2, HMGCR and PCSK9 in comparison to the control diet, however, fisetin did not further elicit any changes in mRNA levels of the same genes. The high fat diet dramatically increased the transcript levels of CYP7A1, which was subsequently reversed by the fisetin. In HepG2 cells, fisetin was found to increase the levels of a nuclear form of SREBP2 and LDLR. In conclusion, fisetin supplementation displayed hypocholesterolemic effects by modulating the expression of genes associated with cholesterol and bile acid metabolism.

To test the hypothesis that urinary metabolites characterizing heart failure (HF) are associated with the magnitude of echocardiographic measurements and ultimately the severity of HF.Patients with systolic HF (n=46) and control subjects (n=32) participated in this study. Patients with type 2 diabetes mellitus were excluded. Echocardiographic measurements were performed, and selected urinary metabolites were quantified.Urinary levels of acetate (p0.05), acetone (p0.01), cytosine (p0.001), methylmalonate (p0.001), and phenylacetylglycine (p0.01) were significantly higher, while 1-methylnicotinamide (p0.05) were significantly lower in HF patients than in controls. There were significant differences in E/E' (p0.05), urinary levels of acetate (p0.005), acetoacetate (p0.05), acetone (p0.05) and ketones (p0.01) according to the New York Heart Association (NYHA) classification in HF patients. Multiple linear regression analysis revealed that urinary ketones were found to be independent factors for both left ventricular ejection fraction and E/E' after adjusting for confounders.Our results showed that urinary levels of ketone bodies are associated with the magnitude of echocardiographic parameters.

In the present study, we hypothesized that onion peel extract (OPE) alters hepatic gene expression to improve blood cholesterol profiles. To investigate the effect of OPE to test our hypothesis, Sprague-Dawley rats were fed ad libitum for 8 weeks with the control, high-fat diet (HFD) or the high-fat diet with 0.2% OPE supplementations (HFD + OPE). Messenger RNA (mRNA) levels of genes in cholesterol metabolism and fatty acid metabolism were examined by semiquantitative reverse transcriptase polymerase chain reaction. The OPE in HFD reverted high fat-induced reduction in mRNA levels of sterol regulatory element-binding protein-2, low-density lipoprotein receptor, and hydroxyl-3-methylglutaryl coenzyme reductase genes in the liver comparable with the levels of the control group. Onion peel extract slightly increased stearoyl-coA desaturase 1 (SCD-1) expression compared with high-fat feeding. However, sterol regulatory element-binding protein-1c and fatty acid synthase were not affected by high-fat or OPE feeding. Onion peel extract also enhanced expression of ATP-binding cassette transporter A1, peroxisome proliferator-activated receptor γ2 and scavenger receptor class B type I genes when compared with high-fat feeding. However, OPE did not influence high fat-triggered changes in apolipoprotein A1 mRNA levels and liver X receptor α were not affected by either high-fat or OPE feeding. Our results suggest that OPE changes the expression of genes associated with cholesterol metabolism in favor of lowering blood low-density lipoprotein cholesterol and enhancing high-density lipoprotein cholesterol through increasing mRNA abundance of low-density lipoprotein receptor and ATP-binding cassette transporter A1 genes.

Quercetin, an abundant flavonol found in fruits and vegetable, has been implicated in lowering the risk of cardiovascular disease that is often associated with high plasma levels of low density lipoprotein (LDL) cholesterol. Here we investigated whether quercetin could modulate the expression of LDL receptors (LDLR) in HepG2 cells and the possible underlying mechanisms to exert quercetin's effects. We found that quercetin was able to induce LDLR expression with at least a 75 µ m concentration, which was accompanied by an increase in nuclear sterol regulatory element binding protein 2 (SREBP2). This effect was mediated by activation of c-jun-N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) signalling pathways as implicated by experiments using chemical inhibitors of each pathway. When cells were challenged with protein synthesis inhibitors in quercetin-activated LDLR transcription, LDL mRNA levels were not significantly affected by cycloheximide but puromycin abolished quercetin-induced LDLR transcription. Taken together, we conclude that quercetin can initiate LDLR transcription by enhancing SREBP2 processing, but new protein synthesis might be necessary to exert a maximum effect of quercetin in the up-regulation of the LDLR gene. Our findings demonstrate that quercetin strongly up-regulated LDLR gene expression, which might elicit hypolipidemic effects by increasing the clearance of circulating LDL cholesterol levels from the blood.

Cell-penetrating peptides (CPPs), including TAT-CPP, have been used to deliver exogenous proteins into living cells. Although a number of proteins fused to TAT-CPP can be delivered into various cells, little is known about the proteolytic cleavage of TAT-fusion proteins in cells. In this study, we demonstrate that a small heat shock protein (sHSP), alphaB-crystallin (αB-crystallin), delivered by TAT-CPP is susceptible to proteolytic cleavage by matrix metalloproteinase-1 (MMP-1) in cardiac myoblast H9c2 cells. Recombinant TAT-αB-crystallin was efficiently transduced into H9c2 cells. For a few hours following protein transduction, generation of a 14-kDa fragment, a cleavage band of TAT-αB-crystallin, increased in a time-dependent manner. This fragment was observed only in detergent-insoluble fractions. Interestingly, treatment with MMP inhibitors blocked the cleavage of TAT-αB-crystallin. In test tubes, recombinant MMP-1 processed TAT-αB-crystallin to generate the major cleavage fragment 14-kDa, as observed in the cells treated with TAT-αB-crystallin. The N-terminal sequences of the 14-kDa fragment were identified as Leu-Arg-Ala-Pro-Ser-Trp-Phe, indicating that this fragment is generated by cleavage at Phe54-Leu55 of αB-crystallin. The MMP-1-selective inhibitor abolished the production of 14-kDa fragments in cells. In addition, the cleaved fragment of TAT-αB-crystallin was significantly reduced in cells transfected with MMP-1 siRNA. Moreover, the enzymatic activity of MMP-1 was markedly increased in TAT-αB-crystallin-treated cells. TAT-αB-crystallin has a cytoprotective effect on H9c2 cells under hypoxic insult, moreover, MMP-1-selective inhibitor treatment led to even increased cell viability. These results suggest that MMP-1 is responsible for proteolytic cleavage of TAT-αB-crystallin during its intracellular transduction in H9c2 cells.

Objective Obesity is a serious health problem implicated in many metabolic disorders (i.e., hypertension, dyslipidemia, and cardiovascular disease). We examined whether the mRNA of tested genes were linked to blood lipid concentrations and vascular endothelial function as features of obesity. Methods In healthy subjects (30–69 y old; normal weight, n = 22, body mass index 18.5–23 kg/m 2 ; overweight, n = 25, body mass index ≥23 kg/m 2 ) the following parameters were measured in the blood circulation: total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triacylglycerol, apolipoprotein AI, apolipoprotein B, adiponectin, high-sensitivity C-reactive protein, and soluble intercellular adhesion molecule-1. The mRNA levels of genes (arginase I [ ARG1 ], very low-density lipoprotein receptor [ VLDLR ], adiponectin receptor-1 [ ADIPOR1 ], ADIPOR2 , and nitric oxide synthase-3 [ NOS3 ]) were tested in the subjects' peripheral blood mononuclear cells. Results The expression levels of all tested genes were investigated for their associations with the blood concentrations of each parameter. In the expression study, only ARG1 (4.5-fold) and VLDLR (4-fold) expressions were significantly upregulated in the overweight group compared with the normal-weight group. The ARG1 mRNA levels were positively associated with blood concentrations of total cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and soluble intercellular adhesion molecule-1. The VLDLR mRNA levels showed a positive relation with triacylglycerol and glucose concentrations and a negative relation with adiponectin levels. Conclusion Significant upregulations of ARG1 and VLDLR were observed in the overweight condition and their expression levels are likely to be closely linked to the phenotypic biomarkers for obesity (disturbed lipid profiles and endothelial dysfunction).

Gene transfer of basic fibroblast growth factor (bFGF) has been shown to induce significant endothelial migration and angiogenesis in ischemic disease models. Here, we investigate what factors are secreted from skeletal muscle cells (SkMCs) transfected with bFGF gene and whether they participate in endothelial cell migration. We constructed replication-defective adenovirus vectors containing the human bFGF gene (Ad/bFGF) or a control LacZ gene (Ad/LacZ) and obtained conditioned media, bFGF-CM and LacZ-CM, from SkMCs infected by Ad/bFGF or Ad/LacZ, respectively. Cell migration significantly increased in HUVECs incubated with bFGF-CM compared to cells incubated with LacZ-CM. Interestingly, HUVEC migration in response to bFGF-CM was only partially blocked by the addition of bFGF-neutralizing antibody, suggesting that bFGF-CM contains other factors that stimulate endothelial cell migration. Several proteins, matrix metalloproteinase-1 (MMP-1), plasminogen activator inhibitor-1 (PAI-1), and cathepsin L, increased in bFGF-CM compared to LacZ-CM; based on 1-dimensional gel electrophoresis and mass spectrometry. Their increased mRNA and protein levels were confirmed by RT-PCR and immunoblot analysis. The recombinant human bFGF protein induced MMP-1, PAI-1, and cathepsin L expression in SkMCs. Endothelial cell migration was reduced in groups treated with bFGF-CM containing neutralizing antibodies against MMP-1 or PAI-1. In particular, HUVECs treated with bFGF-CM containing cell-impermeable cathepsin L inhibitor showed the most significant decrease in cell migration. Cathepsin L protein directly promotes endothelial cell migration through the JNK pathway. These results indicate that cathepsin L released from SkMCs transfected with the bFGF gene can promote endothelial cell migration.

We examined the effects of quercetin-rich onion peel extract supplementation on adipokine expressions from adipose tissues in a diet-induced obese animal model. Male Sprague-Dawley rats (n = 24) were randomly assigned into control (n = 8), high fat diet (HF, n = 8) and high fat diet with onion peel extract (HFOE, n = 8). After 8 weeks, serum biochemical parameters, weights of adipose tissues (epididymal, perirenal and mesenteric fats) and adipokine mRNA levels (adiponectin, IL (interleukin)-6 and visfatin) along with PPAR (peroxisome proliferator-activated receptor) γ2 from adipose tissues were measured. After the 8 week supplementation, mesenteric fat weights were lower in the HFOE group than the HF group (p 0.05). Adiponectin mRNA levels (mesenteric fats) were remarkably higher in the HFOE group than the other groups (p 0.05 for both). Levels of PPARγ2 mRNA (mesenteric fats) were significantly higher in the HF group (p 0.05) than those in the control group, but those in the HFOE group were not different from those in the control group. The IL-6 mRNA levels (perirenal and mesenteric fats) were higher in the HF and HFOE groups, but those in the HFOE group were slightly lower than those in the HF group. In conclusion, quercetin-rich onion peel extract supplementation influenced adipokine expressions, particularly from mesenteric fat, addressing the modulatory effect of this substance on obesity-induced inflammation.

We sought to identify metabolic pathways characterizing human heart failure (HF) using ¹NMR based urinary metabolomic analysis in conjunction with multivariate statistics.Patients with systolic HF of ischemic origin (n=15) and healthy controls (n=20) participated in this study. Patients with type 2 diabetes mellitus were excluded.The results showed that the urine of the HF patients had higher levels of metabolites for acetate (p0.05) and acetone (p0.01) compared to the healthy controls. In addition, there was a perturbation in methylmalonate metabolism as shown by increased urinary levels of methylmalonic acid (p0.001) in the HF patients. HF patients also had increased urinary levels of cytosine (p0.01) and phenylacetylglycine (p0.01) and decreased 1-methylnicotinamide (p0.05) compared to healthy controls.TCA cycle metabolites and fatty acid metabolism were modified in the HF patients, indicating altered energy metabolism. Moreover, perturbations of metabolism in nucleotide and methylmalonate were observed.

Although omega-3 polyunsaturated fatty acids are known to have beneficial effects on cardiovascular diseases, their prognostic value has not been studied prospectively in patients with acute myocardial infarction (AMI).The plasma levels of phospholipids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (% of total fatty acids), were measured in 508 patients (365 males; mean age, 63 years) with AMI. Clinical and biomarker predictors of all-cause and cardiovascular mortality were identified by stepwise Cox regression model. During a mean follow-up of 16.1 months, 36 (7.1%) patients died. After controlling for confounding variables, age (hazard ratio (HR): 1.09, P0.001), renal insufficiency (HR: 2.84, P=0.01) and EPA level (HR: 0.29, P=0.004) were identified as independent predictors of all cause-mortality. When stratified by gender, age (HR: 1.08, P=0.001) and renal insufficiency (HR: 4.49, P=0.003) were predictors of all-cause-mortality in males, whereas EPA level (HR: 0.18, P=0.009) and angiotensin-converting enzyme inhibitor use (HR: 0.24, P=0.03) were identified as predictive of all-cause-mortality in females.Lower plasma level of EPA, but not DHA, was an independent predictor for all-cause-mortality in patients with AMI, but this relationship was significant only in female patients.

A number of studies have investigated peripheral inflammatory indices, including plasma cytokines and related molecules according to subtypes of dementia, but not in mild cognitive impairment (MCI). In this study, we used multiplex cytokine assay to assess the plasma levels of 22 cytokines in patients with MCI subtyped as amnestic and non-amnestic, according to cognitive features. When comparing the levels of plasma growth factors, chemokines and cytokines, plasma levels of monocyte chemotactic protein 3 (MCP-3), and beta-nerve growth factor (beta-NGF) in these two groups, they were found to be significantly higher in amnestic MCI patients than in non-amnestic MCI patients, after adjusting for age and gender. This suggests that plasma MCP-3 and beta-NGF may be useful in differentiating subtypes of MCI.

It has been suggested that the metabolic syndrome (MetS) is associated with increased risk for heart failure (HF) and progression of HF. However, the underlying mechanisms are unclear. We tested whether the presence of the MetS would be associated with the increased degree of inflammatory state in HF.Ninety-one eligible consecutive stable HF patients participated in this cross-sectional study. Anthropometric measurements were carried out and serum concentrations of lipoproteins, apolipoproteins (apoB, apoAI) and high sensitivity C-reactive protein (hsCRP) were measured. The simultaneous measurement of 17 cytokines using bioplex analysis was used.Thirty-five subjects (39% of total, 48% of males and 31% of females) were classified as having the MetS in total HF patients. Serum concentrations of apoB (p0.005) were significantly higher and the ratio of apoAI and apoB was significantly lower (p0.01) in HF patients with MetS than those without MetS. Plasma levels of IL-8 (p0.05) were significantly higher in HF patients with MetS than those without MetS. In addition, serum concentrations of hsCRP (p0.005) were significantly higher in HF patients with MetS compared to those without MetS.The MetS in HF is associated with increased degree of inflammation, which provides information regarding the relationship between inflammation and HF with MetS.

According to the cytokine hypothesis of depression, cytokines play key roles in the behavioral, neuroendocrinal, and neurochemical features of depression. In this study, we used a bioplex assay to simultaneously measure the levels of 23 plasma cytokines in 18 patients with late-life depression and 38 normal controls, and these levels were compared between the two groups. The plasma interleukin-1alpha (IL-1alpha) levels were found to be significantly different between the two groups. After adjusting for age, gender, low-density lipoprotein cholesterol, and triglyceride, the plasma IL-1alpha levels were significantly higher in the patients with late-life depression than in the normal control subjects. Thus, this study provides preliminary evidence that plasma IL-1alpha may play important roles in the pathogenesis of late-life depression.

Inflammatory mechanisms within the central nervous system contribute to cognitive impairment via cytokine-mediated interactions between neurons and glial cells. Sixty-nine subjects were consecutively recruited from October 2005 to February 2007. Fifteen individuals were excluded from the study and we ultimately enrolled 19 not cognitively impaired subjects, 25 mild cognitive impairment patients, and 10 Alzheimer's disease patients. To examine the inflammatory markers of mild cognitive impairment and Alzheimer's disease, we measured the plasma concentrations of 23 cytokines using a bioplex assay. The results showed that the macrophage migration inhibitory factor was higher in mild cognitive impairment and in Alzheimer's disease patients compared with the not cognitively impaired group; the results also showed that monokine induced by gamma interferon was higher in Alzheimer's disease patients than in not cognitively impaired subjects, as well as those of the mild cognitive impairment group [corrected].

Low-fat, high-carbohydrate (LFHC) diets have been shown to increase plasma concentrations of lipoprotein(a) [Lp(a)] and of triacylglycerol- rich lipoproteins (TRLs).We tested whether increases in plasma Lp(a) induced by an LFHC diet are related to changes in TRLs.Healthy men (study 1; n = 140) consumed for 4 wk each a high-fat, low-carbohydrate diet (HFLC; 40% fat, 45% carbohydrate) and an LFHC diet (20% fat, 65% carbohydrate). Plasma lipids; lipoproteins; apolipoprotein (apo) B, A-I, and C-III; and Lp(a) were measured at the end of each diet. In a second group of men following a similar dietary protocol (study 2; n = 33), we isolated apo(a)-containing particles by immunoaffinity chromatography and determined the concentrations of apo C-III in ultracentrifugally isolated subfractions of apo B-containing lipoproteins.In study 1, plasma concentrations of Lp(a) (P0.001), triacylglycerol (P0.001), apo B (P0.005), apo C-III (P0.005), and apo C-III in apo B-containing lipoproteins (non-HDL apo C-III) (P0.001) were significantly higher with the LFHC diet than with the HFLC diet. Stepwise multiple linear regression analysis showed that the association of changes in Lp(a) with changes in non-HDL apo C-III was independent of changes in body mass index, apo B, LDL cholesterol, and HDL cholesterol. Plasma lipid and lipoprotein changes were similar in study 2, and we found that both total apo C-III and the apo C-III content of apo(a)-containing particles were increased in a TRL fraction consisting predominantly of large VLDL particles [TRL-apo(a)].The increase in plasma Lp(a) with an LFHC diet is significantly associated with an increase in non-HDL apo C-III. Enrichment of TRL-apo(a) with apo C-III may contribute to this dietary effect on Lp(a) concentrations.

This study aimed to investigate if glycated hemoglobin (HgbA1C) as compared to fasting blood glucose is better for reflecting cardiometabolic risk in non-diabetic Korean women. Fasting glucose, HgbA1C and lipid profiles were measured in non-diabetic women without disease (n = 91). The relationships of fasting glucose or HgbA1C with anthropometric parameters, lipid profiles, and liver and kidney functions were analyzed. Both fasting glucose and HgbA1C were negatively correlated with HDL-cholesterol (r = -0.287, p = 0.006; r = -0.261, p = 0.012), and positively correlated with age (r = 0.202, p = 0.008; r = 0.221, p = 0.035), waist circumference (r = 0.296, p = 0.005; r = 0.304, p = 0.004), diastolic blood pressure (DBP) (r = 0.206, p = 0.050; r = 0.225, p = 0.032), aspartate transaminase (AST) (r = 0.237, p = 0.024; r = 0.368, p < 0.0001), alanine transaminase (ALT) (r = 0.296, p = 0.004; r = 0.356, p = 0.001), lipid profiles including triglyceride (r = 0.372, p < 0.001; r = 0.208, p = 0.008), LDL-cholesterol (r = 0.315, p = 0.002; r = 0.373, p < 0.0001) and total cholesterol (r = 0.310, p = 0.003; r = 0.284, p = 0.006). When adjusted for age and body mass index, significant relationships of DBP (r = 0.190, p = 0.049), AST (r = 0.262, p = 0.018), ALT (r = 0.277, p = 0.012), and HDL-cholesterol (r = -0.202, p = 0.049) with HgbA1C were still retained, but those with fasting glucose disappeared. In addition, the adjusted relationships of LDL-cholesterol and total cholesterol with HgbA1C were much greater than those with fasting glucose. These results suggest that glycated hemoglobin may be a better predictor than fasting glucose for cardiometabolic risk in non-diabetic Korean women.

Background and Purpose Low-density lipoprotein (LDL) particle size is considered to be one of the more important cardiovascular risk factors, and small LDL particles are known to have atherogenic potential. The aim of this study was to determine whether LDL particle size is associated with stroke severity and functional outcome in patients with atherothrombotic stroke. Methods Between January 2009 and May 2011, 248 patients with first-episode cerebral infarction who were admitted to our hospital within 7 days after symptom onset were prospectively enrolled. LDL particle size was measured using the nondenaturing polyacrylamide gradient gel electrophoresis assay. Stroke severity was assessed by applying the National Institutes of Health Stroke Scale (NIHSS) at admission. Functional outcome was investigated at 3 months after the index stroke using the modified Rankin Scale (mRS), and poor functional outcome was defined as an mRS score of ≥3. Results The LDL particle size in the 248 patients was 25.9±0.9 nm (mean±SD). LDL particle size was inversely correlated with the degree of cerebral artery stenosis (p=0.010). Multinomial multivariate logistic analysis revealed that after adjustment for age, sex, and variables with p

Recently, a subtype of obesity characterized as a metabolically healthy but obese (MHO) individual has been identified. However, limited data are available on these MHO individuals’ metabolic and inflammatory profiles, and the effect of weight loss on these profiles. We investigated metabolic and inflammatory markers in MHO women to determine the effects of a 12-week weight loss on those markers. One hundred and twenty-nine overweight-obese Korean women participated for 12 weeks in a clinical intervention study involving a 300 kcal/day intake reduction. The subjects were divided into two groups: MHO and metabolically abnormal obese (MAO) individuals. Computed tomography was performed. C-reactive protein (CRP), interkeukin-6 (IL-6) and oxidized low-density lipoprotein (LDL), as well as blood lipids, glucose and insulin concentrations were determined at baseline and after weight loss. At baseline, plasma CRP (P

Background: Plasma leptin has been suggested to be involved in the proatherogenic process by increasing oxidative stress. We investigated the relationship between leptin and plasma conjugated diene formation, a measure of LDL oxidation in vivo in schoolchildren. Methods: We measured blood lipid profiles, plasma antioxidant vitamins, leptin and diene conjugation in LDL of 118 Korean children (35 overweight-obese vs. 83 normal weight children). Results: The overweight-obese children showed significantly higher levels of leptin (p < 0.0001), conjugated dienes (p = 0.02), total cholesterol (p < 0.05), triglyceride (p < 0.005) and LDL cholesterol (p < 0.01) and a significantly lower level of plasma lycopene (p < 0.0001) compared with the normal weight children. When all the subjects were classified into the three groups by tertiles of leptin levels, significant differences in circulating conjugated dienes (p < 0.05), lipid-corrected lycopene (p < 0.05), total cholesterol (p < 0.05), triglyceride (p < 0.05) and LDL cholesterol (p < 0.05) were found among the three groups. Conclusion: Our results showed that leptin was positively associated with the LDL conjugated diene formation, which might be related to the proatherogenic process in schoolchildren.

The effect of simvastatin on DNA damage in hypercholesterolemic patients was investigated, and the relationship between the C242T polymorphism of the NADPH oxidase p22phox gene and the antioxidant effects of simvastatin was examined.Simvastatin (20-40 mg /day) was administered for 8 weeks in 72 hypercholesterolemic patients. DNA damage in lymphocytes was quantified using single-cell gel electrophoresis (COMET assay) by measuring tail DNA (%), tail length (microm) and tail moment (tail length x % tail DNA/100).Simvastatin significantly reduced DNA damage as expressed by tail DNA (%, p0.001), tail length (mum, p0.001) and tail moment on the DNA in lymphocytes (p0.001) after 8 weeks. The frequencies of the C242T genotypes for CC, TC, and TT were 75.0%, 23.6% and 1.4% in the subjects. In the presence of the 242T allele, there were higher levels of baseline DNA damage and also a greater improvement in the DNA damage after 8 week simvastatin treatment compared with the CC homozygotes.Simvastatin significantly reduced DNA damage of hypercholesterolemic patients. This study showed that simvastatin has a beneficial effect on the improvement of DNA damage in patients with the 242T allele of NADPH oxidase p22phox gene.

Previous studies have demonstrated that thiamine (vitamin B1) has a cytoprotective effect against ischemic damage to the heart, and that heat shock protein 70 (Hsp70) is capable of protecting cardiac cells from lethal ischemia/hypoxia. We show here that thiamine has a cytoprotective effect on cultured neonatal rat cardiomyocytes under hypoxic insult, and also protects the cardiomyocytes against hypoxia-induced apoptosis; caspase-3 activation, PARP cleavage and DNA fragmentation are all inhibited. Moreover, it increases the level of Hsp70 protein in the cardiomyocytes even under prolonged hypoxic stress and its effects on hypoxia-induced cardiac cell death are antagonized by an Hsp70 inhibitor. These results suggest that the cytoprotective effect of thiamine in cardiomyocytes under hypoxic stress is due to its ability to induce Hsp70.

In this paper, the GaN poly crystal was grown by hydride vapor phase epitaxy at 1090 °C on the metallic compound graphite substrate with good heat dissipation. The coefficient of thermal expansion of the metallic compound graphite substrate is 6.2 µm/(m·K). The heat conductivity is 150 W/(m·K), and specific gravity is 3.1. The metallic compound graphite substrate was gained higher thermal conductivity more than the sapphire substrate through by injecting the nonferrous metal in the porosity carbon graphite base. The GaN poly crystal grown along the [0001] c-axis by hydride vapor phase epitaxy was observed on the metallic compound graphite substrate through the scanning electron microscope and energy dispersive spectroscopy. And electrical characteristic of substrate with each different condition was investigated by Hall Effect measurement.

We studied GaN nanorods grown by hydride vapour phase epitaxy processes to identify optimal growth conditions that yield nanorods appropriate for use in nanodevices. The growth temperature was varied over the range 625–670 °C, and the morphology of the samples changed with increasing growth temperature. GaN nanorods formed at growth temperatures of 645 °C on a Si(111) substrate. At a fixed growth temperature of 645 °C, the HCl:NH3 gas flow ratio was adjusted from 1:37 to 1:41. GaN nanorods with a small diameter of 26 nm formed at a HCl:NH3 ratio of 1:38. Individual GaN nanorods clearly grew along the axial direction, perpendicular to the substrate. Cathodoluminescence measurements at room temperature revealed a red shift as the acceleration energy was increased to 15 keV, possibly associated with the internal electric field.