To clarify the possibility of a preventive effect of dietary vinegar on blood pressure, long-term administration of vinegar or the acetic acid to SHR was examined. As a result, it was observed that ...acetic acid itself, the main component of vinegar, ignificantly reduced both blood pressure (p<0.05) and renin activity (p<0.01) compared to controls given no acetic acid or vinegar, as well as vinegar. There were no significant differences in angiotensin I-converting enzyme activity in various organs. As for the mechanism of this function, it was suggested that this reduction in blood pressure may be caused by the significant reduction in renin activity and the subsequent decrease in angiotensin 2. From this study, it was also suggested that the antihypertensive effect of vinegar is mainly due to the acetic acid in it.
Apoptosis and necrosis occur in nonalcoholic steatohepatitis (NASH) and are thought to be related to fibrosis. A stroke-prone spontaneously hypertensive (SHRSP5/Dmcr) rat fed a high-fat-cholesterol ...(HFC) diet exhibited similar pathological features to human NASH with severe liver fibrosis. We aimed to reveal the molecular pathway and to confirm the relationship between cell death, fibrosis and K18Asp396 levels, a neoepitope generated during cleavage of keratin 18 by caspases, as a candidate for biomarker of hepatic damage in this animal model.
Male rats were fed with control and HFC diets for 2, 8 and 14weeks. Liver apoptosis cells, necrosis score, and the molecular mechanism and K18Asp396 levels were investigated.
HFC diet increased TUNEL-positive cells only at 2weeks and necrosis scores strongly in the livers of rats during the entire period. This diet increased hepatic Bax/Bak but decreased Bcl-2/Bcl-xl expression during the entire period; however, it upregulated caspase 8, 9, and 3/7 activities only at 2weeks, but downregulated them at 14weeks. Additionally, this diet did not increase hepatic cytochrome c expression. Serum K18Asp396 levels have a positive correlation with necrosis score.
In SHRSP5/Dmcr rats, HFC diet caused hepatocyte necrosis rather than apoptosis by the downregulation of all caspase activity. Serum K18Asp396 levels may be a good biomarker of hepatocyte necrosis.
The CDKAL1 gene is among the best-replicated susceptibility loci for type 2 diabetes, originally identified by genome-wide association studies in humans. To clarify a physiological importance of ...CDKAL1, we examined effects of a global Cdkal1-null mutation in mice and also evaluated the influence of a CDKAL1 risk allele on body mass index (BMI) in Japanese subjects.
In Cdkal1-deficient (Cdkal1⁻/⁻) mice, we performed oral glucose tolerance test, insulin tolerance test, and perfusion experiments with and without high-fat feeding. Based on the findings in mice, we tested genetic association of CDKAL1 variants with BMI, as a measure of adiposity, and type 2 diabetes in Japanese.
On a standard diet, Cdkal1⁻/⁻ mice were modestly lighter in weight than wild-type littermates without major alterations in glucose metabolism. On a high fat diet, Cdkal1⁻/⁻ mice showed significant reduction in fat accumulation (17% reduction in %intraabdominal fat, P = 0.023 vs. wild-type littermates) with less impaired insulin sensitivity at an early stage. High fat feeding did not potentiate insulin secretion in Cdkal1⁻/⁻ mice (1.0-fold), contrary to the results in wild-type littermates (1.6-fold, P<0.01). Inversely, at a later stage, Cdkal1⁻/⁻ mice showed more prominent impairment of insulin sensitivity and glucose tolerance. mRNA expression analysis indicated that Scd1 might function as a critical mediator of the altered metabolism in Cdkal1⁻/⁻ mice. In accordance with the findings in mice, a nominally significant (P<0.05) association between CDKAL1 rs4712523 and BMI was replicated in 2 Japanese general populations comprising 5,695 and 12,569 samples; the risk allele for type 2 diabetes was also associated with decreased BMI.
Cdkal1 gene deletion is accompanied by modestly impaired insulin secretion and longitudinal fluctuations in insulin sensitivity during high-fat feeding in mice. CDKAL1 may affect such compensatory mechanisms regulating glucose homeostasis through interaction with diet.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Adult height is a highly heritable, classic polygenic trait. The recent advent of genome-wide association studies has led to the identification of robust association at common variants influencing ...the normal variation of height; the number of loci has now risen to 50. The present study tested the potential overlap of height associations at 46 loci that were previously reported in European-descent populations with those among 1530 Japanese subjects and also attempted to replicate the suggestive association signals that were previously reported in East Asians alone. We found a total of 20 independent loci to be significantly (P<0.05) associated with height among the Japanese subjects (N< or =6814); 19 loci were originally identified in Europeans and the remaining 1 locus (ZFAT) was previously reported in Koreans (P=3.8 x 10(-9) with the Japanese and Korean data combined for ZFAT). Although 41% (19 of 46) of the loci were nominally replicated, a higher proportion of the tested loci seemed to overlap between the Japanese and Europeans; 83% (38 of 46) of the loci showed a concordant direction of association between the two ethnic groups. Despite the substantial inter-population overlap observed in the present study, further investigation is warranted to search for loci with enhanced genetic impacts in East Asians than in Europeans.
Dietary anthocyanins are widely distributed in fruits, vegetables and red wines, and there are several reports mentioning their beneficial effects. Previously we reported that cyanidin-3-glucoside ...(Cy3G) induced endothelial nitric oxide synthase (eNOS) expression and nitric oxide (NO) production in bovine vascular endothelial cells. In the present study, we show that Cy3G regulates phosphorylation of eNOS and Akt, affects the interaction between eNOS and soluble guanylyl cyclase, and increases cyclic guanosine monophosphate (cGMP) production. Our results suggest that Cy3G enhances vascular eNOS activity, and may help to improve vascular endothelial function.
Eicosapentaenoic acid (EPA) can ameliorate certain liver lesions involved in non-alcoholic steatohepatitis (NASH). A previous study has found that stroke-prone spontaneously hypertensive 5/Dmcr ...(SHRSP5/Dmcr) rats fed a high fat-cholesterol (HFC) diet developed fibrotic steatohepatitis with histological similarities to NASH. This study evaluated the potential effects and mechanisms of action of EPA supplementation using this rodent model.
Male rats were randomly assigned to groups that were fed with either the stroke-prone (SP) diet or HFC diet with or without EPA for 2, 8 and 14weeks, respectively. The liver histopathology, biochemical features, mRNA and protein levels, and nuclear factor-κB (NF-κB) DNA binding activity were determined.
The SP diet-fed rats presented normal livers. Conversely, the HFC diet-fed rats developed microvesicular/macrovesicular steatosis, inflammation, ballooning degeneration and severe fibrosis. At 2weeks, the administration of EPA inhibited hepatic inflammatory recruitment by blocking the phosphorylation of inhibitor of κB-α (IκBα), which antagonizes the NF-κB activation pathway. The dietary supplementation of EPA for 8weeks ameliorated hepatic triglyceride accumulation and macrovesicular steatosis by inhibiting the HFC diet-induced decrease in the protein levels of enzymes involved in fatty acid β-oxidation including carnitine palmitoyltransferase 1, very long chain acyl-CoA dehydrogenase and peroxisomal bifunctional protein. Although the administration of EPA elicited no histologically detectable effects on severe fibrosis at 14weeks, it restored an HFC diet-induced decline in hepatic adenosine triphosphate (ATP) levels and suppressed ballooning degeneration, suggesting that EPA may inhibit HFC diet-induced ATP loss and cell death.
Initial amelioration of the inflammation and steatosis in the rats after EPA supplementation indicates a possibility to treat steatohepatitis. Additionally, this study provides new insights into the roles of EPA in hepatic ATP depletion and subsequent hepatocellular injury during severe fibrosis.
Since our previous report on WHO CARDIAC Study data demonstrated that 24-hour urinary (24U) taurine (Tau) excretion was a useful biomarker of seafood (SF) intake and inversely related to the ...mortality rates of stroke and coronary heart diseases in the world, we determined that SF is important in the risk reduction of lifestyle related-diseases. The amounts of dietary SF intake are so far estimated from a nutritional survey or 24U Tau excretion.The sodium/potassium ratio of spot urine (SU) and the 24U ratio were reported to be significantly correlated with. Therefore, we presently examined the relationship of Tau excretion in the morning SU with 24U Tau for simplifying the population comparison and the follow-up of SF intake changes in the process of food education program (FEP).
After informed consent was obtained, 54 children aged 6-11 years (Children) and 193 adolescents aged 13-18 years (Adolescents) participated in collecting precisely 24U and SU of the first urination on the same day and answered the questionnaire including age and height and weight measurements. The urine samples were measured for creatinine (Cre) and Tau, and the association of these between 24U and SU were analyzed.
The success rates of 24U sampling were very high in Children and Adolescents, 96.4% and 82.4%, respectively. From the result of the multiple regression analysis of SU Tau/Cre and weight we obtained formulas for predicting 24U Tau excretion in Children and Adolescents as follows: Children: 24U Tau = 16.3 (weight) + 314.3 (SU Tau/Cre) -175.2; and Adolescents: 24U Tau = 20.2 (weight) + 644.7 (SU Tau/Cre) - 569.4.
The present study established the regression equation to estimate 24U Tau excretion from SU Tau/Cre and weight. These formulas are expected to contribute to the estimation of fish and SF intake and the follow-up of the change of the dietary behavior by FEP in Children and Adolescents.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Nutritional and pharmacological factors are needed to prevent bone loss that occurs with increasing age. The chemical compounds that act on bone metabolism as nutrients in food, however, are poorly ...understood. The effect of resveratrol, a natural phytoestrogen, on the proliferation and differentiation of osteoblastic MC3T3-E1 cells was studied. Resveratrol dose-dependently increased DNA synthesis (10−9−10−7M) of MC3T3-E1 cells. In addition, resveratrol increased alkaline phosphatase (ALP) activity and prolyl hydroxylase activity of MC3T3-E1 cells (10−6−10−5M). Moreover, the antiestrogen tamoxifen eliminated the stimulation of MC3T3-E1 cells on the proliferation and ALP activity by resveratrol. On the other hand, resveratrol inhibited prostaglandin E2production in MC3T3-E1 cells (10−8−10−6M). Our present study is the first to demonstrate that resveratrol directly stimulates cell proliferation and differentiation of osteoblasts.
Environmental and genetic factors influence serum total homocysteine (tHcy), a risk factor for vascular diseases. The gene polymorphism of methylenetetrahydrofolate reductase (MTHFR) is reported to ...be a genetic factor for influencing tHcy. However, it is not clear whether MTHFR polymorphism influences tHcy in the younger generation. To investigate the influence of MTHFR polymorphism on vascular disease risks in young Japanese females, we determined dietary intakes, serum folate and tHcy, and examined the influence of MTHFR 677C>T polymorphism in healthy junior and high school students (n=192, 12-18y). The relationships between MTHFR polymorphism and folate intake, serum folate or tHcy were investigated by dividing participants into CC, CT and TT types. Among individuals with the TT genotype, folate and tHcy levels were significantly lower (p<0.05) or higher (p<0.0001), respectively, than in those with the other genotypes; although there were no significant differences in the intake of folate among genotypes. In addition, a significant inverse correlation between folate and tHcy (p<0.05) was noted in all genotypes, even in young females, so far not examined in Asian populations. Therefore, MTHFR genotypes were proven to be a significant determinant for folate and tHcy concentrations. However, the association of increased folate intake with lower tHcy concentration, even in cases of the mutation TT type, indicates the importance of folate intake in young Japanese females for early detection of risk, as well as the prevention of vascular diseases.
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