[Vitamins and Immune System Health].

Keeping the immune system healthy forms an effective way to fight infections. Past experience has shown that, in addition to effective interventions including vaccination, drug therapy, and non-pharmaceutical intervention (NPI), dietary nutrition and mental health are also key factors in maintaining immune system health and combating emerging and sudden outbreaks of infections. As the main dietary nutrients, vitamins are active regulators of the immune response and exert a critical impact on the immunity of the human body. Vitamin deficiency causes increased levels of inflammation and decreased immunity, which usually starts in the oral tissues. Appropriate vitamin supplementation can help the body optimize immune function, enhance oral immunity, and reduce the negative impact of pathogen infection on the human body, which makes it a feasible, effective, and universally applicable anti-infection solution. This review focuses on the immunomodulatory effects of vitamin A, B, C, D, and E and proposes that an omics-based new systemic approach will lead to a breakthrough of the limitations in traditional single-factor single-pathway research and provide the direction for the basic and applied research of vitamin immune regulation and anti-infection in all aspects.

Self-reported health problems related to traditional dietary practices in postpartum women from urban, suburban and rural areas of Hubei province, China: the 'zuò yuèzi'.

BACKGROUND AND OBJECTIVES: We aimed to investigate the prevalence of maternal health problems in the postpartum period and their association with traditional Chinese postpartum diets and behaviours in three selected regions in Hubei province, China. METHODS AND STUDY DESIGN: A cross-sectional study was conducted in urban, suburban and rural areas. A total of 2100 women who had given birth to full-term single infants in the past two years were enrolled. Their postpartum diet, personal behaviours, and health problems were surveyed by trained interviewers. RESULTS: During the puerperium women consumed plentiful eggs, fish, poultry and meats; however, fruit, vegetable and milk consumption were limited. A high prevalence of health problems potentially related to pregnancy and the puerperium were found. At least one such problem was reported by 59.3% of women. The putative postpartum problems were backaches (29.6%), arthralgia or leg clonus (12.7%), breast problems (19.6%), constipation (18.7%), haemorrhoids (11.7%), dizziness or headaches (14.8%), anaemia (10.0%). Multiple logistic regression analysis showed that leafy vegetable intake and frequent recipe change in the puerperium were positively associated with less anal diseases. Bathing or hair washing did not increase the risk of maternal infection as belief would have suggested. However, bathing was a risk factor for backache or arthralgia, and tooth brushing was a risk factor for bleeding gums. Excessive housework was a risk factor for anal diseases and disordered uterine involution. CONCLUSION: Postpartum maternal health problems were prevalent in Hubei province. These were in part associated with postpartum traditional Chinese diets and behaviours.

Analysis of trans-resveratrol and trans-piceid in vegetable foods using high-performance liquid chromatography.

Trans-resveratrol and resveratrol glucoside are natural phenolic compounds existed in a wide variety of plant species, which are extensively consumed in many countries. The existing studies excessively focused on grapes and their products, and little about daily vegetable foods. Actually, in much more countries, vegetable foods are residents' principal food and nutrient origins. This study was to investigate the levels of trans-resveratrol and trans-piceid in daily vegetable foods of China using high-performance liquid chromatography (HPLC) method with fluorescence detection (FLD). Trans-piceid was the major form existing in most vegetable foods, and most of the samples contained higher trans-piceid than trans-resveratrol. The contents of trans-resveratrol and trans-piceid in different varieties and regions were different. Moreover, peculiar vegetable foods to some region were also one of the most important sources of trans-resveratrol and trans-piceid. Therefore, vegetable foods were other significant sources of trans-resveratrol and trans-piceid except the foods published.

Ameliorative effects of lutein on non-alcoholic fatty liver disease in rats.

AIM: To investigate the therapeutic effects of lutein against non-alcoholic fatty liver disease (NAFLD) and the related underlying mechanism. METHODS: After 9 d of acclimation to a constant temperature-controlled room (20 °C-22 °C) under 12 h light/dark cycles, male Sprague-Darley rats were randomly divided into two groups and fed a standard commercial diet (n = 8) or a high-fat diet (HFD) (n = 32) for 10 d. Animals receiving HFD were then randomly divided into 4 groups and administered with 0, 12.5, 25, or 50 mg/kg (body weight) per day of lutein for the next 45 d. At the end of the experiment, the perinephric and abdominal adipose tissues of the rats were isolated and weighed. Additionally, serum and liver lipid metabolic condition parameters were measured, and liver function and insulin resistance state indexes were assessed. Liver samples were collected and stained with hematoxylin eosin and Oil Red O, and the expression of the key factors related to insulin signaling and lipid metabolism in the liver were detected using Western blot and real-time polymerase chain reaction analyses. RESULTS: Our data showed that after being fed a high-fat diet for 10 d, the rats showed a significant gain in body weight, energy efficiency, and serum total cholesterol (TC) and triglyceride (TG) levels. Lutein supplementation induced fat loss in rats fed a high-fat diet, without influencing body weight or energy efficiency, and decreased serum TC and hepatic TC and TG levels. Moreover, lutein supplementation decreased hepatic levels of lipid accumulation and glutamic pyruvic transaminase content, and also improved insulin sensitivity. Lutein administration also increased the expression of key factors in hepatic insulin signaling, such as insulin receptor substrate-2, phosphatidylinositol 3-kinase, and glucose transporter-2 at the gene and protein levels. Furthermore, high-dose lutein increased the expression of peroxisome proliferators activated receptor-α and sirtuin 1, which are associated with lipid metabolism and insulin signaling. CONCLUSION: These results demonstrate that lutein has positive effects on NAFLD via the modulation of hepatic lipid accumulation and insulin resistance.

Lutein prevents high fat diet-induced atherosclerosis in ApoE-deficient mice by inhibiting NADPH oxidase and increasing PPAR expression.

Epidemiological and experimental studies provide supportive evidence that lutein, a major carotenoid, may act as a chemopreventive agent against atherosclerosis, although the underlying molecular mechanisms are not well understood. The main aim of this study was to investigate the effects of lutein on the alleviation of atherosclerosis and its molecular mechanisms involved in oxidative stress and lipid metabolism. Male apolipoprotein E knockout mice (n = 55) were fed either a normal chow diet or a high fat diet (HFD) supplemented with or without lutein for 24 weeks. The results showed that a HFD induced atherosclerosis formation, lipid metabolism disorders and oxidative stress, but noticeable improvements were observed in the lutein treated group. Additionally, lutein supplementation reversed the decreased protein expression of aortic heme oxygenase-1 and increased the mRNA and protein expressions of aortic nicotinamide-adenine dinucleotide phosphate oxidase stimulated by a HFD. Furthermore, the decreased mRNA and protein expression levels of hepatic peroxisome proliferator-activated receptor-α, carnitine palmitoyltransferase 1A, acyl CoA oxidase 1, low density lipoprotein receptors and scavenger receptor class B type I observed in mice with atherosclerosis were markedly enhanced after treatment with lutein. Taken together, these data add new evidence supporting the anti-atherogenic properties of lutein and describing its mechanisms of action in atherosclerosis prevention, including oxidative stress and lipid metabolism improvements.

Alteration of lipid profile in subclinical hypothyroidism: a meta-analysis.

BACKGROUND: Previous studies yielded controversial results about the alteration of lipid profiles in patients with subclinical hypothyroidism. We performed a meta-analysis to investigate the association between subclinical hypothyroidism and lipid profiles. MATERIAL AND METHODS: We searched PubMed, Cochrane Library, and China National Knowledge Infrastructure articles published January 1990 through January 2014. Dissertation databases (PQDT and CDMD) were searched for additional unpublished articles. We included articles reporting the relationship between subclinical hypothyroidism and at least 1 parameter of lipid profiles, and calculated the overall weighted mean difference (WMD) with a random effects model. Meta-regression was used to explore the source of heterogeneity among studies, and the Egger test, Begg test, and the trim and fill method were used to assess potential publication bias. RESULTS: Sixteen observational studies were included in our analysis. Meta-analysis suggested that the serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and total triglyceride levels were significantly increased in patients with subclinical hypothyroidism compared with euthyroidism individuals; the WMD were 12.17 mg/dl, 7.01 mg/dl, and 13.19 mg/dl, respectively (P<0.001 for all). No significant difference was observed for serum high-density lipoprotein cholesterol (HDL-C). Match strategy was the main source of heterogeneity among studies in TC and LDL-C analysis. Potential publication bias was found in TC and LDL-C analysis by the Egger test or Begg test and was not confirmed by the trim and fill method. CONCLUSIONS: Subclinical hypothyroidism may correlate with altered lipid profile. Previous studies had limitations in the control of potential confounding factors and further studies should consider those factors.

Iodine excess induces hepatic steatosis through disturbance of thyroid hormone metabolism involving oxidative stress in BALB/c mice.

Iodine excess is emerging as a new focus. A better understanding of its hazardous effects on the liver will be of great benefit to health. The aim of this study is to illustrate the effects of iodine excess on hepatic lipid homeostasis and explore its possible mechanisms. One hundred twenty BaLB/c mice were given iodine at different levels (0, 0.3, 0.6, 1.2, 2.4, and 4.8 mg I/L) in drinking water for 1 or 3 months. Lipid parameters and serum thyroid hormones were measured. Hepatic type 1 deiodinase activity and oxidative stress parameters were evaluated. The mRNA expression of sterol regulatory element-binding protein-1c (SREBP-1c) and fatty acid synthase (FAS) was detected by real-time polymerase chain reaction. Dose-dependent increase of hepatic triglyceride content was detected (r = 0.680, P < 0.01) in iodine-loaded groups. Evident hepatic steatosis was observed in 2.4 and 4.8 mg I/L iodine-loaded groups. The activities of antioxidant enzymes (glutathione peroxidase and superoxide dismutase) were decreased, and the malondialdehyde level was increased by excessive iodine in both serum and liver in a dose-dependent manner, accompanying the decrease of hepatic D1 activity. That resulted in the increase of serum total thyroxine and the decrease of serum total triiodothyronine in iodine-loaded groups. The mRNA expression of SREBP-1c and FAS was increased in iodine-loaded groups in response to the change of serum triiodothyronine. Present findings demonstrated that iodine excess could dose dependently induce hepatic steatosis. Furthermore, our data suggested that the disturbance of thyroid hormone metabolism involving oxidative stress may play a critical role in iodine excess-induced hepatic steatosis.

[Exploratory study on the association between different iodine nutrition and the prevalence of dyslipidemia in Shenzhen City].

OBJECTIVE: To investigate the association between different iodine nutrition and the prevalence of dyslipidemia in a representative sample of subjects in Shenzhen. METHOD: A total of 326 adults from 2 different communities in Shenzhen were included in the study. A questionnaire, physical examination and laboratory test were given to all subjects. 317 questionnaires and blood samples were effective. RESULTS: When the urine iodine concentration was less than 200 microg/L, there is a reverse relationship between iodine nutrition and prevalence of HDL-c (r(s) = - 0.164, P = 0.031). When the urine iodine concentration was higher than 300 microg/L, there is a positive relationship between iodine nutrition and prevalence of HDL-c (r(s) = 0.246, P = 0.013). There was no significant correlation between other lipid parameters and urinary iodine concentration. Multivariate Logistic regression analysis showed that high blood glucose and abdominal obesity were significantly related to the prevalence of dyslipidemia, urine iodine concentration was no significant correlation with the prevalence of dyslipidemia. CONCLUSION: The prevalence of dyslipidemia in Shenzhen is high, there may be a U shaped relationship between iodine nutrition and the prevalence of abnormal HDL-c level.

Leucine facilitates insulin signaling through a Gαi protein-dependent signaling pathway in hepatocytes.

In this study, we addressed the direct effect of leucine on insulin signaling. In investigating the associated mechanisms, we found that leucine itself does not activate the classical Akt- or ERK1/2 MAP kinase-dependent signaling pathways but can facilitate the insulin-induced phosphorylations of Akt(473) and ERK1/2 in a time- and dose-dependent manner in cultured hepatocytes. The leucine-facilitated insulin-induced phosphorylation of Akt at residue 473 was not affected by knocking down the key component of mTORC1 or -2 complexes but was blocked by inhibition of c-Src (PP2), PI3K (LY294002), Gαi protein (pertussis toxin or siRNA against Gαi1 gene, or ß-arrestin 2 (siRNA)). Similarly, the leucine-facilitated insulin activation of ERK1/2 was also blunted by pertussis toxin. We further show that leucine facilitated the insulin-mediated suppression of glucose production and expression of key gluconeogenic genes in a Gαi1 protein-dependent manner in cultured primary hepatocytes. Together, these results show that leucine can directly facilitate insulin signaling through a Gαi protein-dependent intracellular signaling pathway. This is the first evidence showing that macronutrients like amino acid leucine can facilitate insulin signaling through G proteins directly.

Chronic leucine supplementation increases body weight and insulin sensitivity in rats on high-fat diet likely by promoting insulin signaling in insulin-target tissues.

SCOPE: This study investigated the effect of chronic leucine supplementation on insulin sensitivity and the associated mechanisms in rats on high-fat diet (HFD). METHODS AND RESULTS: Male Sprague-Dawley rats were fed either normal chow diet or HFD supplemented with 0, 1.5, 3.0, and 4.5% leucine for 24 weeks. We found that chronic leucine supplementation increased insulin sensitivity together with increased body weight in rats on HFD, but had no effect on insulin sensitivity in rats on normal chow diet. The increased insulin sensitivity by leucine supplementation was not associated with altered ectopic fat accumulation in liver and muscle, plasma levels of lipids and cytokines, but is associated with reduced oxidative stress and improved insulin signaling. Chronic leucine supplementation did not enhance insulin receptor substract-1 (IRS-1) phosphorylation on serine 302, but elevated basal IRS-1 phosphorylation on tyrosine 632 and improved insulin-stimulated protein kinase B (Akt) and mammalian target of rapamycin (mTOR) phosphorylation in liver, skeletal muscle, and adipose tissue of rats on HFD rats, indicating leucine supplementation prevented HFD-induced insulin resistance in insulin-target tissues. CONCLUSION: Chronic leucine supplementation can increase insulin sensitivity and body weight likely by reducing oxidative stress and improving insulin signaling pathway in rats on HFD.

Alleviative effects of resveratrol on nonalcoholic fatty liver disease are associated with up regulation of hepatic low density lipoprotein receptor and scavenger receptor class B type I gene expressions in rats.

Lipid metabolic disorders are widely considered to be one of the most critical and basic link in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). The aim of this study was to illustrate the alleviation function of resveratrol (Res) on NAFLD and the roles of hepatic fatty acid synthase (FAS), low density lipoprotein receptor (LDLr), scavenger receptor class B type I (SR-BI), and thyroid hormone receptor ß1 (TRß1), which are the key molecules involved in lipid metabolism. Adult male Wistar rats were fed a normal diet or high fat/sucrose diet (HFS) with or without resveratrol for 13 weeks. HFS induced NAFLD formation and increased the lipids concentrations in serum and livers of rats, while noticeable improvement has been reached by Res intervention. Moreover, Res protected against HFS-induced decrease in hepatic LDLr and SR-BI mRNA and protein expressions, whereas TRß1 expressions were impervious with/without Res. Unexpectedly, hepatic FAS gene expressions were markedly diminished in NAFLD rats and were gradually increased by treatment with Res. These data indicate that the alleviative effects of Res on NAFLD are associated with up regulation of hepatic LDLr and SR-BI gene expressions, which provide new insights into the pharmacological targets of Res in the prevention of NAFLD.

Resveratrol ameliorates high-glucose-induced hyperpermeability mediated by caveolae via VEGF/KDR pathway.

Endothelial hyperpermeability induced by hyperglycemia is the initial step in the development of atherosclerosis, one of the most serious cardiovascular complications in diabetes. In the present study, we investigated the effects of resveratrol (RSV), a bioactive ingredient extracted from Chinese herb rhizoma polygonum cuspidatum, on permeability in vitro and the molecular mechanisms involved. Permeability was assessed by the efflux of fluorescein isothiocyanate (FITC)-dextran permeated through the monolayer endothelial cells (ECs). The mRNA levels, protein expressions, and secretions were measured by quantitative real-time PCR, western blot, and ELISA, respectively. Increased permeability and caveolin-1 (cav-1) expression were observed in monolayer ECs exposed to high glucose. Resveratrol treatment alleviated the hyperpermeability and the overexpression of cav-1 induced by high glucose in a dose-dependent manner. ß-Cyclodextrin, a structural inhibitor of caveolae, reduced the hyperpermeability caused by high glucose. Resveratrol also down-regulated the increased expressions of vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR, or VEGF receptor-2) induced by high glucose. Inhibition of VEGF/KDR pathway by using SU5416, a selective inhibitor of KDR, alleviated the hyperpermeability and the cav-1 overexpression induced by high glucose. The above results demonstrate that RSV ameliorates caveolae-mediated hyperpermeability induced by high glucose via VEGF/KDR pathway.

Resveratrol reduces vascular cell senescence through attenuation of oxidative stress by SIRT1/NADPH oxidase-dependent mechanisms.

OBJECTIVE: Senescence of vascular cells contributes to the development of cardiovascular diseases and the overall aging. This study was undertaken to investigate the effects of resveratrol (Res) on amelioration of vascular cell aging and the role of SIRT1/nicotinamide adenine dinucleotide phosphate (NADPH) oxidase pathway. METHODS AND RESULTS: Adult male Wistar rats were treated with a high-fat/sucrose diet (HFS) in the presence or absence of Res for 3 months. HFS and in vitro treatment with high glucose increased the senescence cells and reactive oxygen species production in rat aorta and cultured bovine aortic endothelial cells (BAECs), respectively, which was attenuated by Res treatment. Res protected against HFS- or high-glucose-induced increase in NADPH oxidase p47phox expression and decrease in SIRT1 level. Apocynin, a NADPH oxidase inhibitor, down-regulated p47phox protein expression, but had no influence on SIRT1 protein; sirtinol, a SIRT1 inhibitor, aggravated the decrease in SIRT1 protein level and the increase in p47phox protein expression induced by high glucose. CONCLUSION: Our studies suggested that Res was able to reverse the senescence process in aorta induced by HFS in rats or induced by the exposure to high glucose in cultured BAECs. The underlying mechanism is at least SIRT1/NADPH oxidase pathway dependent.

Excess iodine and high-fat diet combination modulates lipid profile, thyroid hormone, and hepatic LDLr expression values in mice.

The aim of this study was to illustrate the combined effect of excess iodine and high-fat diet on lipid metabolism and its potential molecular mechanism. Sixty Balb/c mice were randomly allocated to three control groups or three excess iodine groups and fed with a high-fat diet in the absence or presence of 1,200 µg/L iodine for 1, 3, or 6 months, respectively. Serum lipid parameters and serum thyroid hormones were measured. Expressions of scavenger receptor class B type-I (SR-BI) and low density lipoproteins receptor (LDLr) mRNA and protein in liver were detected. Thyroid histology and liver type 1 iodothyronine deiodinase activity were analyzed. At the end of 3 and 6 months, compared with control, serum TC, TG, and LDL-C in excess iodine group were significantly lower (p < 0.05). LDLr expression in liver was increased significantly (p < 0.05) and parallel to the change of serum TC and TG. TT3 and TT4 levels in serum were elevated and TSH decreased significantly (p < 0.05). Liver type I iodothyronine deiodinase activity was significantly higher (p < 0.05) than control at the end of 6 months. Moreover, a time course damage effect of excess iodine combined with high-fat diet on thyroid glands was observed. The present findings demonstrated that excess iodine combined with high-fat diet could cause damage to thyroid glands and lead to thyroid hormone disorder. Those in turn caused the upregulation of hepatic LDLr gene, which resulted in the disorder in serum lipids.

Biphasic effects of chronic ethanol exposure on insulin-stimulated glucose uptake in primary cultured rat skeletal muscle cells: role of the Akt pathway and GLUT4.

BACKGROUND: mild or moderate chronic alcohol intake has been shown to be associated with increased insulin sensitivity, while chronic alcohol abuse demonstrates a contrary effect. The mechanism underlying this biphasic effect has not yet been clarified. We investigated whether chronic ethanol exposure mediates biphasic changes on insulin sensitivity and whether the phosphatidylinositol 3-kinase/Akt pathway is involved in vitro. METHODS: primary cultured rat skeletal muscle cells were exposed to ethanol (0-400 mM) for 24 h. Insulin sensitivity was assessed by the (3) H-labelled 2-deoxyglucose uptake assay. Phosphatidylinositol 3-kinase, cytosol and cell membrane glucose transporter-4 (GLUT4), as well as the Akt phosphorylated form, were analyzed by Western blots. RESULTS: biphasic effects of ethanol on insulin sensitivity were observed in primary cultured skeletal muscle cells in a dose-dependent manner. Compared with the untreated group, 50 and 100 mM concentrations of ethanol resulted in a significant increase in 2-deoxyglucose uptake by 29 and 28%, respectively, while higher concentrations of ethanol (200, 400 mM) showed a significant decrease in 2-deoxyglucose uptake by 28 and 47%, respectively. The changes in glucose transport activity were in line with the changes in Akt Ser473 phosphorylation and GLUT4 expression in an ethanol dose-dependent biphasic manner. The phosphorylation of Akt and GLUT4 protein contents were up-regulated after treatment with low concentrations of ethanol (50, 100 mM) and down-regulated with high concentrations of ethanol (200, 400 mM) for 24 h. CONCLUSION: ethanol mediates biphasic changes on insulin sensitivity at least in part via the Akt pathway and GLUT4 expression.

Supplemental selenium alleviates the toxic effects of excessive iodine on thyroid.

As excessive iodine intake is associated with a decrease of the activities of selenocysteine-containing enzymes, supplemental selenium was hypothesized to alleviate the toxic effects of excessive iodine. In order to verify this hypothesis, Balb/C mice were tested by giving tap water with or without potassium iodate and/or sodium selenite for 16 weeks, and the levels of iodine in urine and thyroid, the hepatic selenium level, the activities of glutathione peroxidase (GSHPx), type 1 deiodinase (D1), and thyroid peroxidase (TPO) were assayed. It had been observed in excessive iodine group that hepatic selenium, the activities of GSHPx, D1, and TPO decreased, while in the groups of 0.2 mg/L, 0.3 mg/L and 0.4 mg/L supplemental selenium, the urinary iodine increased significantly. Compared with the group of excessive iodine intake alone, supplemental selenium groups had higher activities of GSHPx, D1, and TPO. We could draw the conclusion that supplemental selenium could alleviate toxic effect of excessive iodine on thyroid. The optimal dosage of selenium ranges from 0.2 to 0.3 mg/L which can protect against thyroid hormone dysfunction induced by excessive iodine intake.

Dose and time-dependent hypercholesterolemic effects of iodine excess via TRbeta1-mediated down regulation of hepatic LDLr gene expression.

BACKGROUND: With the global improvement of iodine nutrition, iodine excess is emerging as a new concern. AIM OF STUDY: The aim of this study is to illustrate the physiological effects and potential molecular mechanisms of excessive iodine intake on lipid metabolism. METHODS: Balb/c mice were given drinking water containing different levels of iodine for 1 month and treated with 1.2 microg/mL iodine for different periods of time, respectively. Plasma lipid parameters and serum thyroid hormones were measured. Expressions of hepatic genes were detected by real-time polymerase chain reactions and Western blot. RESULTS: Dose-dependent hypercholesterolemic effects were detected in mice (TC, r = 0.615; p < 0.01). Drinking 1.2 microg/mL iodine water for 1 month had no significant effect on serum lipid metabolism, while prolonged exposure induced an increase of serum cholesterol. Serum thyroid hormones were not affected by iodine throughout the study. At the molecular level, we detected a dose-dependent attenuation of hepatic low density lipoprotein receptor (LDLr) and thyroid hormone receptor beta1 (TRbeta1) expression in parallel to the change of serum cholesterol. Treatment with 1.2 microg/mL iodine water for 1 month did not affect LDLr and TRbeta1 expression, while 3 or 6 months exposure resulted in a decrease of their expression. CONCLUSION: Present findings demonstrated dose- and time-dependent hypercholesterolemic effects of iodine excess. Furthermore, our data suggests that TRbeta1-mediated down regulation of hepatic LDLr gene may play a critical role in iodine excess-induced hypercholesterolemic effects.

Association between heme oxygenase-1 gene promoter polymorphisms and type 2 diabetes in a Chinese population.

The authors aimed to determine whether 2 functional polymorphisms in the heme oxygenase-1 (HO-1) gene promoter are associated with type 2 diabetes mellitus (T2DM). A Chinese case-control study involving 1,103 newly diagnosed T2DM patients, 371 patients with impaired glucose regulation (IGR), and 1,615 controls was performed (December 2004-December 2007). A (GT)(n) microsatellite polymorphism and a single nucleotide polymorphism, T(-413)A, were genotyped, and their functional relevance was evaluated by examining the level of HO-1 protein expression. For the (GT)(n) microsatellite polymorphism, genotypes with the L (GT)(n) allele (>or=25 GT repeats) were associated with increased odds of IGR or T2DM compared with the S/S genotype (<25 GT repeats) (S/L genotype: odds ratio (OR) = 1.35, P = 0.048; L/L genotype: OR = 1.65, P = 0.006). Subsequent haplotype analysis showed that haplotype TL contributed to increased odds of IGR or T2DM compared with haplotype TS (OR = 1.56, P = 0.003). In functional analyses, HO-1 expression level was significantly reduced in persons with IGR and T2DM carrying the L/L (GT)(n) genotype compared with persons with the S/S genotype. Further haplotype combination assay confirmed the functional dominance of the (GT)(n) microsatellite polymorphism over the T(-413)A single nucleotide polymorphism. These results support an association between the HO-1 (GT)(n) microsatellite polymorphism, HO-1 expression levels, and the odds of T2DM.

Green tea polyphenols inhibit plasminogen activator inhibitor-1 expression and secretion in endothelial cells.

Compelling epidemiological evidence suggests that the consumption of green tea is associated with beneficial effects in prevention of cardiovascular diseases. Plasminogen activator inhibitor-1 (PAI-1) is known to play a pivotal role in cardiovascular diseases including arteriosclerosis and hypertension. Increased PAI-1 was found in atherosclerotic lesions, and high PAI-1 plasma levels were associated with coronary heart disease. To determine the effect and molecular mechanism of green tea polyphenols (GTPs) on the regulation of PAI-1 expression in endothelial cells, bovine aortic endothelial cells were incubated with GTPs, and PAI-1 expressions were measured by western blot and enzyme-linked immunosorbent assay, respectively. GTPs significantly reduced PAI-1 expression and secretion in a time-dependent and dose-dependent manner. Inhibition of phosphatidylinositol 3-kinase (PI3K) with wortmannin markedly reversed GTPs repression of PAI-1 expression. In addition, the GTP-induced inhibitory effect was associated with an increased of activation of the protein kinase Akt. These results suggest that GTPs inhibit PAI-1 expression and its release from endothelial cells through the PI3K/Akt pathway, which may contribute to cardiovascular protection.

Impaired ghrelin response after high-fat meals is associated with decreased satiety in obese and lean Chinese young adults.

Ghrelin and peptide tyrosine tyrosine (PYY) are known to affect appetite and body weight, but the acute effects of fat-rich and carbohydrate-rich meals on plasma ghrelin, PYY response, and appetite remain unclear. We hypothesized that obese individuals had impaired postprandial ghrelin and PYY response based on macronutrient content of meals, affecting appetite and energy intake. We conducted a randomized crossover trail comparing fasting ghrelin and PYY concentrations, postprandial ghrelin and PYY responses, and subjective appetite in 15 obese and 12 lean Chinese young adults after they consumed isocaloric high-carbohydrate [HC; 88% energy carbohydrate, 4% energy fat, 8% energy protein] and high-fat (HF; 25% energy carbohydrate, 71% energy fat, 4% energy protein) meals. Ghrelin concentrations over time differed between HC and HF meals (P < 0.01) via repeated measures of ANOVA, with lower postprandial ghrelin suppression after HF meals, especially among obese participants. PYY response differed between meals among lean participants, with a delayed and higher postprandial PYY peak after the HF meal (P < 0.01); however, PYY response did not differ among obese participants. The incremental area under the curve of PYY was higher in lean than in obese participants after the HF meal (P < 0.01). These results suggest that impaired ghrelin response after HF meals may contribute to reduced satiety and overeating, especially among obese individuals. Whether an attenuated response of PYY in obese participants after a HF meal bears any physiological consequences warrants further study.