A Mouse Model of Metabolic Syndrome; Increase in Visceral Adipose Tissue Precedes the Development of Fatty Liver and Insulin Resistance in High-Fat Diet-Fed Male KK/Ta Mice

To determine the relative contribution of obesity and visceral white adipose tissue (WAT) to metabolic syndrome, we developed a model that is susceptible to high-fat diet-induced obesity and insulin resistance using male KK/Ta mice. The ratio of WAT weight to body weight was greater in the high-fat diet group compared with the control group in 10-, 14-, and 22-week-old mice. The increase in visceral WAT preceded development of fatty liver and insulin resistance. Adiponectin mRNA expression in WAT was markedly decreased before the decrease in its plasma levels or the development of insulin resistance. Insulin resistance appeared in association with fatty infiltration and TNF-α expression in the liver in 22-week-old mice. These data indicate that our mouse model would be useful for future studies that investigate the role of visceral WAT and its products in the development of metabolic syndrome

Bofutsushosan, an Oriental Herbal Medicine, Attenuates the Weight Gain of White Adipose Tissue and the Increased Size of Adipocytes Associated with the Increase in Their Expression of Uncoupling Protein 1 in High-Fat Diet-Fed Male KK/Ta mice

Bofutsushosan (BOF), an oriental herbal medicine, has been used as an anti-obesity drug in overweight patients. In the present study, to evaluate the anti-obesity and anti-diabetic effects of BOF, we investigated the effects of BOF on the white adipose tissue (WAT) weight, the size of adipocytes, adiponectin expression, and oral glucose tolerance test results in high-fat diet-fed male KK/Ta mice. In addition, the mRNA expression levels of uncoupling protein 1 (UCP1) and UCP2 mRNA in WAT and brown adipose tissue (BAT) were measured. 6-week-old KK/Ta mice were divided into four groups and fed a purified powdered basal diet (the BD group), a purified high-fat (HF) powdered diet containing suet powder at 37.5 g/100 g diet (the HF group), a high-fat diet plus 1.0% bofutsushosan (BOF) treatment (the HF + BOF group), or a high-fat diet plus 1.0% daisaikoto (DAI) treatment (the HF + DAI group) for 4 weeks. The weight of WAT and the size of adipocytes were increased in the HF group compared with those in the BD group, and these increases in the HF group were significantly inhibited in the HF + BOF group, but not affected in the HF + DAI group. There were no statistically significant differences in plasma levels and tissue mRNA levels of adiponectin among the four groups. There were no significant differences in UCP1 mRNA expression of BAT among the four groups. The expression of UCP1 mRNA in WAT was found in the HF + BOF group, but little expression was seen in the WAT of the BD, HF, or HF + DAI groups. The elevated plasma glucose levels and responses after the glucose loading in the HF group tended to decrease in the HF + BOF group. These results suggest that BOF decreases the weight and size gains of WAT along with up-regulating UCP1 mRNA in WAT in high-fat diet-fed mice

a proton pump inhibitor, mediates anti-inflammatory effect in gastric mucosal cells through the induction of heme oxygenase-1 via activation of NF-E2-related factor 2 and oxidation of kelch-like ECH-associating protein 1

ABSTRACT Induction of heme oxygenase-1 (HO-1) expression has been associated with cytoprotective and anti-inflammatory actions of lansoprazole, a proton pump inhibitor, but the underlying molecular mechanisms remain largely unresolved. In this study, we investigate the role of transcriptional NF-E2-related factor 2 (Nrf2), its phosphorylation/activation, and oxidation of Kelch-like ECHassociating protein 1 (Keap1) in lansoprazole-induced HO-1 up-regulation using cultured gastric epithelial cells (rat gastric mucosal cell line, RGM-1). HO-1 expression of RGM-1 cells was markedly enhanced in a time-and dose-dependent manner by the treatment with lansoprazole, and this up-regulation of HO-1 contributed to the inhibition of chemokine production from stimulated RGM-1 cells. Transfection of Nrf2-siRNA suppressed the lansoprazole-induced HO-1. An electrophoretic mobility shift assay showed increases in the nuclear translocation and stress-response elements (StRE) binding activity of Nrf2 proteins in RGM-1 cells treated with lansoprazole. Furthermore, in RGM-1 cells transfected with HO-1 enhancer luciferase reporter plasmid containing mutant StRE, lansoprazole-induced HO-1 reporter gene activity was diminished. Lansoprazole promoted the phosphorylation of extracellular signal-regulated kinase (ERK), and lansoprazole-induced HO-1 up-regulation was suppressed by U0126, an ERKspecific inhibitor. Phosphorylated Nrf2 protein was detected in the phosphoprotein fraction purified by a Pro-Q Diamond Phosphoprotein Enrichment kit. Finally, an oxidative form of the Keap1 protein was detected in lansoprazole-treated RGM-1 cells by analyzing S-oxidized proteins using biotinylated cysteine as a molecular probe. These results indicate that lansoprazole up-regulates HO-1 expression in rat gastric epithelial cells, and the upregulated HO-1 contributes to the anti-inflammatory effects of the drug. Phosphorylation of ERK and Nrf2, activation and nuclear translocation of Nrf2, and oxidation of Keap1 are all involved in the lansoprazole-induced HO-1 up-regulation. Proton pump inhibitors (PPIs) such as lansoprazole and omeprazole are extensively used to treat acid-related disorders, including gastroesophageal reflux disease and peptic ulcer disease caused by stress, nonsteroidal anti-inflammatory drugs, and Helicobacter pylori infection. PPIs are stron

塩味感受性に及ぼす玄米食の影響

　食塩の過剰摂取と高血圧症には密接な関係があることが知られている。また、世界的にも日本人の食塩摂取量は多く、我が国の健康増進のために減塩対策は大きな課題である。そこで、本研究では味覚感度の高い若年者を対象に二種類の官能評価を実施した。官能評価Ⅰでは食塩水の濃度差識別を二点識別法で実施し、被験者が濃度比1.06で識別可能であることが示された。また、官能評価Ⅱでは同条件で作成した飯（玄米、精白米）に対する塩味の感じ方を二点比較法で評価し、玄米食の方が塩味を強く感じる（p=0.0137）ことが示された。このことから、玄米食が塩味感受性を増強させることが示唆された