Analysis of an antioxidative defence system of hydrogen peroxide-treated pancreatic islet-derived 1.1B4 cells and siRNA targeting NR4A3-treated cells by microarray.

Pancreatic islet ß-cells weaken under oxidative stress. In this study, human pancreatic islet-derived 1.1B4 cells were exposed to H2O2 and analysed using a human microarray, which revealed that heme oxygenase 1 (HMOX1), glutamate-cysteine ligase, early growth response 1, nuclear receptor subfamily 4 group A member 3 (NR4A3) and jun B proto-oncogene were upregulated, whereas superoxide dismutase 1 and catalase were not. Expression of NR4A3 rapidly increased after H2O2 addition, and the 1.1B4 cells treated with siRNA targeting NR4A3 became sensitive to H2O2; further, HMOX1 expression was strongly inhibited, suggesting that NR4A3 is an oxidative stress-responsive transcription factor that functions through HMOX1 expression in pancreatic islet ß-cells. Expression of cyclin E1 and cyclin-dependent kinase 1 was also inhibited by siRNAs targeting NR4A3.

Curricular evaluation of "SHOKUIKU program" as a postgraduate minor course of food and nutrition education using a text-mining procedure.

BACKGROUND: "SHOKUIKU", food and nutrition education, is a national promotion to enable people to acquire an adequate knowledge of SHOKU (which include food, nutrition, dietary habits, etc.) in Japanese society and to allow people to make appropriate SHOKU choices in Japan. In order to educate SHOKUIKU experts who can promote evidence-based SHOKUIKU with advanced professional knowledge and skills, an original "SHOKUIKU program" was established. To evaluate this program, a short answer questionnaire was given to students. Results were objectively analyzed by text mining procedures. METHODS: Five hundred forty four comment papers submitted by a total of 52 consenting students after each lecture in the 12 omnibus-style lectures were examined as cross-sectional data. A total of 2507 sentences were decomposed into words, and word classes of morpheme in Japanese were properly specified. Subsequently, on the basis of a constructed keyword data base, 123 morphemes with high frequency were investigated with co-occurrence network analysis. Furthermore, multivariate network analyses according to the student's major were performed. RESULTS: Students majoring in food and nutritional sciences recognized that evidence-based SHOKUIKU is "difficult" but "necessary" to "convey" reliable information at "actual" SHOKUIKU sites. On the other hand, students studying other majors not only got an "interesting" opportunity to "learn" "nutrition" and "eating habits" but also thought about their own SHOKUIKU promotion in relation to their major. CONCLUSIONS: These results suggest that the students of the Food Course assumed that they would practice the evidence-based SHOKUIKU themselves, while the students of other courses learned new knowledge more passively. The results also confirmed that students comprehensively grasped the 12 omnibus-style lectures and understood the significance of evidence-based SHOKUIKU regardless of their major. Our original educational program could be valuable for postgraduate students to promote SHOKUIKU.

Oleuropein improves insulin resistance in skeletal muscle by promoting the translocation of GLUT4.

As the beneficial effects of the Mediterranean diet on human health are well established, the phenolic compounds in olive oil have been gaining interest. Oleuropein, a major phenolic compound in olives, is known to reduce the blood glucose levels in alloxan-induced diabetic rats and rabbits, however, its effect on type 2 diabetes caused by obesity is not clear. The purpose of this study is clarifying the effect of oleuropein on the glucose tolerance in skeletal muscle under the condition of lipotoxicity caused by type 2 diabetes. Oleuropein enhanced glucose uptake in C2C12 cells without insulin. Translocation of glucose transporter 4 (GLUT4) into the cell membrane was promoted by activation of adenosine monophosphate-activated protein kinase (AMPK) but not protein kinase B (Akt). Physiological concentration of oleuropein (10 µM) was sufficient to express beneficial effects on C2C12 cells. Oleuropein prevented palmitic acid-induced myocellular insulin resistance. Furthermore, in gastrocnemius muscles of mice fed a high fat diet, oleuropein also induced the GLUT4 localization into cell membrane. These results suggest the possibility of oleuropein to be effective for type 2 diabetes by reducing insulin resistance in skeletal muscles.

Efficacy of habitual exercise for improving lipid profiles depends on the PPRAγ genotype in Japanese males.

Peroxisome proliferator-activated receptor gamma (PPARγ) responds to thiazolidinedione derivatives, which are ligands of PPARγ, and affects insulin resistance. Recently, a PPARγ study reported that in high-fat-diet-induced obesity, the phosphorylation of PPARγ prevented the transcription of specific PPARγ targets that have anti-obesity effects. We previously reported that genetic variants of the fatty acid desaturase were associated with plasma lipid profiles and could contribute to dyslipidemia in Japanese males. The aim of this study was to investigate the anti-obesity effects of PPARγ variants on lipid profiles. One hundred and thirty-eight (138) Japanese males participated in the study. Their serum lipid markers and the fatty acid composition of their red blood cell (RBC) membranes were determined. The stearoyl-CoA desaturase 1 (SCD1) indices were represented as the fatty acid product : precursor ratios. The participants were genotyped for the single-nucleotide polymorphism rs2938392 in the PPARγ gene. The participants' fitness habits were also surveyed by questionnaire. The effects of habitual exercise on the measured lipid parameters were compared in each genotype group. No association between the genotypes in the PPARγ gene and the biochemical data was found. However, the serum triglyceride levels and the SCD1 indices in RBC membranes were significantly higher in the participants who carried the major rs2938392 allele (A/A) and did not habitually exercise than in those who did exercise. These findings indicate that the risk for detrimental lipid profiles in the absence of habitual exercise depends on the PPARγ genotype in Japanese males.

Genetic variants of the fatty acid desaturase gene cluster are associated with plasma LDL cholesterol levels in Japanese males.

Fatty acid (FA) compositions in tissues are related to metabolic disorders, and consequently the appropriate management of underlying FA compositions in tissues is considered to be important. However, the relationship among the serum lipid profiles, the FA composition of the red blood cell (RBC) membranes and genetic variations in the fatty acid desaturase (FADS) genes in Japanese men is unclear. In this study, the subjects recruited were 137 Japanese men, 40 to 60 y old, who had a regular health checkup. Their serum lipid profile and the relative FA composition of the RBC membranes were measured. They were genotyped for the single nucleotide polymorphisms (SNPs) rs174553, rs174546, rs99780 and rs174583 in FADS gene. Multiple regression analysis was conducted to detect the relationship among hyperlipidemia, the FA composition of the RBC and the FADS genotypes. As a result, the homozygous genotype for the minor alleles in rs174553, rs174546, rs99780 were found to be associated with lower low-density lipoprotein cholesterol (LDL-C) levels and a lower LDL-C/total-cholesterol ratio. The homozygous genotype for the minor alleles reduced the risk of high LDL-C level (R2=0.50, ß=-0.20, p=0.009), whereas, the arachidonic acid (AA) levels in the carriers of the homozygous genotype for the minor alleles tended to be lower compared with the carriers of the major alleles. However, no significant differences were observed in any FA level among the three genotypes for four SNPs. These results indicate that the appropriate management of serum LDL-C levels depending on genetic predisposition in FADS genotypes should be encouraged.

Use of high-normal levels of haemoglobin A(1C) and fasting plasma glucose for diabetes screening and for prediction: a meta-analysis.

BACKGROUND: Using high-normal levels of haemoglobin A1C (Abnormal-A1C ) or fasting plasma glucose (FPG) (Abnormal-FPG) for diabetes screening are expected to improve the ability to detect persons with or at high risk of diabetes. We assessed the diagnostic and predictive capacity for diabetes of Abnormal-A1C and Abnormal-FPG. We compared these to the combined use of the two measures to the single use of either measurement. METHODS: We analysed 31 eligible cross-sectional or cohort studies that assessed diagnostic or predictive ability, respectively, by using lower A1C and FPG cutoff values than recommended by current diabetes criteria. Positive and negative likelihood ratios (LR+ and LR-) were calculated to assess the ability to confirm or exclude diabetes, respectively, on the basis of a bivariate random-effects model. RESULTS: With both Abnormal-A1C and Abnormal-FPG, the pooled LR+ was above 4 for diagnosing diabetes and above 3 for predicting diabetes. However, the pooled LR- for predicting diabetes was higher with Abnormal-A1C (0.48) and Abnormal-FPG (0.49) in comparison with that for diagnosing diabetes (0.27, Abnormal-A1C ; 0.28, Abnormal-FPG). In eight studies that assessed the predictive ability of the combination of A1C and FPG, using either Abnormal-A1C or Abnormal-FPG could lower LR- to 0.17 from 0.43 for only Abnormal-A1C and from 0.38 for only Abnormal-FPG. Accordingly, LR+ was also lowered to 2.37 from 3.36 for only Abnormal-A1C and from 3.84 for only-Abnormal-FPG. CONCLUSION: The use of the two blood glucose tests had insufficient capacity to identify subjects at high risk for diabetes but had considerable capacity to identify undiagnosed diabetes.

Quality and accuracy of Internet information concerning a healthy diet.

The Internet is used by many consumers interested in healthy living. The aim of the present study was to explore the variations among Internet information concerning a healthy diet and to evaluate the potential for misleading information. To conduct a descriptive analysis, the search term "healthy diet" was entered into three search engines and the first 100 results were examined. Of the evaluated 48 websites, 5, 26 and 11, respectively, gave references, date when information was updated and cautioned users. For assessment of accuracy, six dietary guidelines were used as references and the website was scored according to the number of recommended dietary features that matched the guidelines. Websites that specified their objectives scored significantly higher when matched with each guideline than the websites that did not state four guidelines (p < 0.05). Internet information on a "healthy diet" was likely to only partially follow recommendations of the guidelines.

Changes in the phospholipid fatty acid composition of the lipid droplet during the differentiation of 3T3-L1 adipocytes.

Lipid droplets (LDs) are independent organelles in adipocytes that are composed of a lipid ester core surrounded by a phospholipid monolayer. The fatty acid composition of the phospholipid monolayer should determine the metabolism and dynamics of LDs. In this study, we examined the fatty acid composition of phospholipid monolayer in LDs during the differentiation of 3T3-L1 adipocytes. The levels of saturated fatty acids (SFAs), such as 16:0 and 18:0, in phosphatidylcholine (PC) and phosphatidylethanolamine (PE) of LDs decreased during differentiation. In contrast, the levels of monounsaturated fatty acids (MUFAs) such as 16:1n-7 and 18:1n-9 in PC and PE of LDs and the level of polyunsaturated fatty acids (PUFAs) such as 20:3n-6, 20:4n-6 and 22:6n-3 in PE of LDs increased during differentiation. These results suggest that the phospholipid monolayer in mature LDs is more fluid than that in nascent LDs. The fatty acid compositions of the LD monolayer were different from those of the microsome bilayer in the early stage of differentiation, but similar to those of the microsome bilayer in the late stage of differentiation. These data provide evidence that biophysical properties of the phospholipid monolayer in LDs change during adipocyte differentiation.

Isolation and antioxidant activity of zeylaniin A, a new macrocyclic ellagitannin from Syzygium zeylanicum leaves.

Methanol extract obtained from Syzygium zeylanicum leaves exhibited potent antioxidant activity. The water extract obtained from this methanol extract by sequential extraction with hexane, chloroform, ethylacetate, and n-butanol also showed the strongest antioxidant activity among extracts. This water extract was further fractionated by column chromatography with various concentrations of methanol solutions. Among the 6 resultant fractions, the fraction developed with 20% methanol exhibited the most potent antioxidant activity. The one peak among the three major HPLC peaks in this fraction was isolated and purified using a preparative HPLC. The structure of a pure compound was elucidated as a novel macrocyclic ellagitannin using a (1)H/(13)C NMR and a high-resolution electrospray ionization mass spectrometer. This newly isolated compound, which was named zeylaniin A, exhibited potent antioxidant activities in the assays of DPPH, oxygen radical absorbance capacity, and malonadehyde/gas chromatography. S. zeylanicum leaves can be a possible source of natural antioxidants.

Fasting and post-challenge glucose as quantitative cardiovascular risk factors: a meta-analysis.

AIM: The post-challenge glucose (PCG) level has been suggested to be superior to the fasting blood glucose (FG) level for predicting the risk of future cardiovascular disease (CVD); however, the extent of its superiority has not been consistently shown among previous cohort studies. Therefore, we conducted a meta-analysis to summarize the quantitative association of FG and PCG with CVD risk and compared the strengths of the two associations. METHOD: Electronic literature searches using MEDLINE and EMBASE with an additional manual search were conducted for prospective observational studies of the association of FG and PCG with CVD risk. Studies were included if they were prospective studies in which the relative risk (RR) of CVD per 1 standard deviation increase in both FG and PCG could be estimated. Pooled relative risks for the incremental increase were calculated as RR(FG) and RR(PCG) using a bivariate random-effects model. RESULT: Data were obtained from 14 eligible studies that included 70,889 participants and 2,927 cases. The pooled RR(FG) and RR(PCG) (95% confidence interval) were, respectively, 1.15 (1.06 to 1.26) and 1.24 (1.12 to 1.36); the difference was significant (P =0.001). The association of PCG with CVD risk was stronger in studies that targeted participants with a baseline mean FG < 100 mg/dl (P < 0.001) or mean age ≥ 55 years (P =0.004). CONCLUSIONS: Overall, the association of PCG with CVD risk was stronger than that of FG by approximately 50% on a log scale. Measuring PCG is especially important in populations with relatively low FG levels or in the elderly, although it is often burdensome in routine clinical practice.

The level of orally ingested vitamin C affected the expression of vitamin C transporters and vitamin C accumulation in the livers of ODS rats.

We investigated the effects of vitamin C administration on vitamin C-specific transporters in ODS/ShiJcl-od/od rat livers. The vitamin C-specific transporter levels increased in the livers of the rats not administered vitamin C and decreased in the livers of those administered vitamin C at 100 mg/d, indicating that these transporter levels can be influenced by the amount of vitamin C administered.

Dose of 3-methylcholanthrene enhances vitamin C accumulation and mRNA expression of its transporter in the liver of ODS rats and in HepG2 cells.

Polycyclic aromatic hydrocarbon (PAH) compounds including 3-methylcholanthrene induce harmful reactive intermediates and reactive oxygen species. This study reports the effect of 3-methylcholanthrene on the accumulation of vitamin C and the expression of vitamin C transporters. ODS rats were given l-ascorbic acid daily and intraperitoneal injections of 10 mg 3-methylcholanthrene in total. On day 10, vitamin C concentrations and the expression of vitamin C transporter in the tissues were measured. As a result, the levels of sodium-dependent vitamin C transporter (SVCTs) 1 and the l-ascorbic acid concentration in 3-methylcholanthrene-treated livers and hepatocytes have increased significantly. However, the content of vitamin C in the urine and TBARS in the liver have not changed. These results suggest that the administration of 3-methylcholanthrene elevates the requirement for vitamin C via (SVCTs) 1 due to xenobitics-metabolizing, such as the induction of cytochrome P450 family.

Antioxidant/anti-inflammatory activities and total phenolic content of extracts obtained from plants grown in Vietnam.

BACKGROUND: Medicinal plants have been used to treat various diseases since ancient times. Their specific activities, such as antioxidant, anti-inflammatory and anti-cancer, have been studied intensively. In particular, plants grown in Vietnam have attracted considerable attention among food chemists as ideal sources of natural medicinal chemicals. RESULTS: The methanol extracts from three edible Vietnamese-grown plants, Tram, Voi and Gac, tested with the DPPH assay showed antioxidant activities of 91.7 ± 0.4, 63.4 ± 0.7 and 3.7 ± 0.1% respectively. The malonaldehyde/gas chromatography assay also revealed strong antioxidant activity in Tram and Voi at a level of 25 µg mL(-1) (95.5 ± 0.3 and 78.5 ± 1.4% respectively). These results were confirmed by the thiobarbituric acid assay. The antioxidant activities correlated positively with the level of total phenolics in all plants. Tram exhibited dose response-related lipoxygenase-inhibitory activity, with values of 74.2 ± 3.1% at 5 µg mL(-1) , 62.0 ± 0% at 0.5 µg mL(-1) and 3.0 ± 1.5% at 0.05 µg mL(-1) . Conversely, Voi and Gac showed negative anti-lipoxygenase activity. CONCLUSION: The antioxidant/anti-inflammatory activities and total phenolic contents of the three edible plants grown in Vietnam revealed that they are good sources of supplements for human health.

Effects of oxygen concentration on the expression of an antioxidant gene in HepG2.

To clarify the effects of O(2) concentration (cO(2)) on antioxidant gene expression in human hepatocytes, mRNA expression of HepG2 cells cultured at 1, 3, and 5% cO(2) and atmospheric gas-phase, was measured. The expression of some genes fluctuated depending on the cO(2) in the incubator. This indicates that cO(2) is a critically important factor in the investigation of human biological mechanisms.

Association of lifestyle factors, polymorphisms in adiponectin, perilipin and hormone sensitive lipase, and clinical markers in Japanese males.

According to recent genome-wide association studies, a number of single nucleotide polymorphisms is reported to be associated with diseases or several clinical markers. Among them, adiponectin (ADIPOQ) and perilipin (PLIN) polymorphisms are major factors of obesity. However, the association between lifestyle factor, these polymorphisms and obesity-related clinical markers in Japanese is not well researched. Therefore, the aim of present study is to investigate the association between lifestyle factor, polymorphisms of lipid metabolic genes, and clinical markers in 148 middle-aged Japanese males. The study revealed that ADIPOQ 45 T>G and ADIPOQ 276 G>T genotypes were significantly associated with triglyceride, total cholesterol, hemoglobin A1c (HbA1c) in blood and body mass index (BMI). PLIN4 11482 G>A and hormone sensitive lipase (LIPE)-60 C>G genotypes were respectively associated with BMI and serum triglyceride. Not only genetic factors but also lifestyle factors influence several clinical markers. The BMI of subjects who like sweets and have the GG allele in ADIPOQ 276 G>T was higher than that of subjects who don't like sweets. The habit of eating fruits and fish affected low-density lipoprotein-cholesterol of the GT allele and HbA1c of the TT allele in ADIPOQ 276 G>T. Those findings indicate improvement and conservation of lifestyle depending on genetic predisposition in ADIPOQ, PLIN and LIPE should be encouraged.

Even low-intensity and low-volume exercise training may improve insulin resistance in the elderly.

OBJECTIVE: Moderate to high intensity exercise training is known to ameliorate the coronary risk factors in relation to an improvement in body composition. However, the benefit of low-intensity and low-volume training for these risk factors remains unclear in elderly people. Therefore, we investigated the effects of low-intensity and low-volume exercise training on blood lipid values and insulin resistance in the elderly. METHODS: A total of 56 healthy elderly individuals (42 females and 14 males) aged 64+/-6 years participated in a 12-week exercise program, comprising aerobic training and resistance training. RESULTS: After the program, there were no significant changes in high-density lipoprotein cholesterol, triglyceride serum levels, or in peak oxygen uptake on average. However, the homeostasis of minimal assessment of insulin resistance (HOMA-IR) value was significantly reduced by 21%. The participants were categorized into tertiles based on initial Body Mass Index (BMI). The Middle-BMI group (non-obese subjects) showed reduced HOMA-IR (2.0-->1.3, P<0.01), but this reduction was not associated with the reduction in BMI (r=0.08, P=0.74), whereas the two reductions were significantly associated in the High-BMI group (r=0.61, P=0.01). CONCLUSION: Even low-intensity and low-volume exercise training, which would ordinarily be insufficient for improving mean lipid values or aerobic fitness, was found to be effective in improving insulin resistance in the elderly. The improvement in insulin resistance was independent of the improvement in obesity.

Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol: a meta-analysis.

BACKGROUND: Aerobic exercise is believed to reduce the risk of cardiovascular disease partially through increasing serum levels of high-density lipoprotein cholesterol (HDL-C). However, this effect varies considerably among exercise intervention studies. METHODS: Electronic database searches of MEDLINE (1966-2005) for randomized controlled trials that examined the effect of exercise training on HDL-C level. RESULTS: Twenty-five articles were included. Mean net change in HDL-C level was statistically significant but modest (2.53 mg/dL [0.065 mmol/L]; P<.001). Minimal weekly exercise volume for increasing HDL-C level was estimated to be 900 kcal of energy expenditure per week or 120 minutes of exercise per week. Univariate regression analysis indicated that every 10-minute prolongation of exercise per session was associated with an approximately 1.4-mg/dL (0.036-mmol/L) increase in HDL-C level. In contrast, there was no significant association between exercise frequency or intensity. Multiple meta-regression analyses demonstrated that subjects with a body mass index (calculated as weight in kilograms divided by height in meters squared) less than 28 and total cholesterol level of 220 mg/dL [5.7 mmol/L] or more experienced an approximately 2.1-mg/dL (0.054-mmol/L) larger increase in HDL-C level than those with a body mass index of 28 or more and total cholesterol level less than 220 mg/dL (5.7 mmol/L). CONCLUSIONS: Regular aerobic exercise modestly increases HDL-C level. There appears to exist a minimum exercise volume for a significant increase in HDL-C level. Exercise duration per session was the most important element of an exercise prescription. Exercise was more effective in subjects with initially high total cholesterol levels or low body mass index.