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Daikenchuto (TU-100) is herbal medicine which predominantly contains ginger, Japanese pepper, and ginseng. We investigated whether TU-100 can affect the composition of gut flora and intestinal tumor development using Apc(Min/+) mice, a murine model of intestinal tumor. Bacterial 16S rRNA sequencing and short-chain fatty acid analysis were performed on faecal samples. Tumor number and size were analysed. Any change in gene expression of the tumor tissues was assessed by real-time PCR. Principal coordinate analysis (PCoA) showed that the faecal microbiota cluster of TU-100-fed mice was different from the microbiota of control mice. However, no significant difference was observed in the concentration of short-chain fatty acids, tumor number, and gene expression levels between the two groups. Our data showed that TU-100 can affect the intestinal environment; however, it does not contribute in tumor progression or inhibition in our setting.

Objective Visceral fat obesity is located upstream of metabolic syndrome and atherosclerotic diseases. Accumulating evidences indicate that several immunocytes including macrophages infiltrate into adipose tissue and induce chronic low-grade inflammation. We recently analyzed the association between visceral fat adiposity and the gene expression profile in peripheral blood cells in human subjects and demonstrated the close relationship of visceral fat adiposity and disturbance of circadian rhythm in peripheral blood cells. In a series of studies, we herein investigated the association of visceral fat adiposity and mRNA levels relating to inflammatory genes in peripheral blood cells. Approach and Results Microarray analysis was performed in peripheral blood cells from 28 obese subjects. Reverse transcription-polymerase chain reaction (RT-PCR) was conducted by using blood cells from 57 obese subjects. Obesity was defined as body mass index (BMI) greater than 25 kg/m2 according to the Japanese criteria. Gene expression profile analysis was carried out with Agilent whole human genome 4 × 44 K oligo-DNA microarray. Gene ontology (GO) analysis showed that 14 genes were significantly associated with visceral fat adiposity among 239 genes relating to inflammation. Among 14 genes, RT-PCR demonstrated that S100A8, S100A9, and S100A12 positively correlated with visceral fat adiposity in 57 subjects. Stepwise multiple regression analysis showed that S100A8 and S100A12 mRNA levels were closely associated with HOMA-IR and S100A9 mRNA was significantly related to adiponectin and CRP. Conclusions Peripheral blood mRNA levels of S100 family were closely associated with insulin resistance and inflammation.

Photoluminescence (PL) properties of CuLa0.98Ln0.02O2 (Ln: lanthanides with incomplete 4f electron shell) with delafossite-type crystal structure have been investigated. It has been elucidated that Ln3+ can be substituted for La3+ site in CuLa0.98Ln0.02O2 with inversion symmetry. PL spectra of CuLa0.98Ln0.02O2 showed intense PL lines due to magnetic dipole transition and weak ones due to electric dipole transition, showing agreement with the selection rule, according to which electric dipole transition should be forbidden by the inversion symmetry around Ln3+ in LaO6 octahedron. It was revealed that the observed PL mainly originated from charge transfer absorption between Ln3+ and O2−, resulting in higher intensity than those of Y2O3:Ln3+. Luminescence of materials with the same delafossite-type crystal structure could be controlled only by the kinds of Ln3+.

Adiponectin, an adipocyte-derived protein abundant in the circulation, is thought to be protective against atherosclerosis. However, it is not fully understood how the association of adiponectin with vascular cells and its antiatherogenic effect are connected. In this study, T-cadherin was essential for accumulation of adiponectin in the neointima and atherosclerotic plaque lesions, and the adiponectin-T-cadherin association protected against vascular injury. In the apolipoprotein E-knockout (ApoE-KO) mice, adiponectin and T-cadherin colocalized on endothelial cells and synthetic smooth muscle cells in the aortic intima. Notably, aortic adiponectin protein disappeared in T-cadherin/ApoE double-knockout (Tcad/ApoE-DKO) mice with significant elevation of blood adiponectin concentration. Furthermore, in Tcad/ApoE-DKO mice, carotid artery ligation resulted in a significant increase of neointimal thickness compared with ApoE-KO mice. Finally, on a high-cholesterol diet, Tcad/ApoE-DKO mice increased atherosclerotic plaque formation, despite a 5-fold increase in plasma adiponectin level compared with that in ApoE-KO mice. In vitro, knockdown of T-cadherin from human aortic smooth muscle cells (HASMCs) with synthetic phenotype significantly reduced adiponectin accumulation on HASMCs and negated the inhibitory effect of adiponectin on proinflammatory change. Collective evidence showed that adiponectin accumulates in the vasculature via T-cadherin, and the adiponectin-T-cadherin association plays a protective role against neointimal and atherosclerotic plaque formations.-Fujishima, Y., Maeda, N., Matsuda, K., Masuda, S., Mori, T., Fukuda, S., Sekimoto, R., Yamaoka, M., Obata, Y., Kita, S., Nishizawa, H., Funahashi, T., Ranscht, B., Shimomura, I. Adiponectin association with T-cadherin protects against neointima proliferation and atherosclerosis.

Smooth CuLa 0.98 Eu 0.02 O 2 thin film has successfully been prepared by pulsed laser deposition method at room temperature. Crystal structure of the obtained film was almost same as that of CuLa 0.98 Eu 0.02 O 2 polycrystalline ceramic. Orange luminescence with high intensity due to 5 D 0 – 7 F 0,1 transitions of Eu 3+ , which was an evidence of Eu 3+ substitution for La 3+ site in LaO 6 octahedra with the inversion symmetry, was also observed in the obtained film. The optical band gap of CuLa 0.98 Eu 0.02 O 2 was measured to be 2.85 eV from absorption spectroscopy.

Obesity is associated with heart failure and cardiac hypertrophy. Adiponectin has been shown to play a protective role for cardiovascular diseases. The β-catenin signaling pathway is deeply involved in cardiac hypertrophy. However, the effect of adiponectin on β-catenin signaling has not been investigated in cardiac hypertrophy. Present study aimed to clarify the involvement of adiponectin and β-catenin signaling pathway in the mouse model of angiotensin II (AngII)-induced cardiac hypertrophy. In hearts of Wild type (WT) mice, AngII dose-dependently augmented cytosolic β-catenin protein level. WT and adiponectin knockout (Adipo-KO) mice were administered with AngII at 2.4 mg/kg/day for 14 days and were also injected with adenovirus expressing the adiponectin (Ad-Adipo) or the β-galactosidase (Ad-βgal). Cardiac mRNA levels relating to hypertrophy and β-catenin signaling were increased in Adipo-KO mice and these changes were reversed by Ad-Adipo. Phosphorylation of Akt was increased in Adipo-KO mice and such increases were reversed by Ad-Adipo. Furthermore, the phosphorylation of glycogen synthase kinase 3β (GSK3β) at Ser(9) and cytosolic β-catenin level were increased in Adipo-KO mice and they were significantly reduced by Ad-Adipo treatment. Phosphorylation of mammalian target of rapamycin (mTOR) was reduced by Ad-Adipo-mediated adiponectin supplementation in WT and Adipo-KO mice. The current study suggests that adiponectin attenuates AngII-induced cardiac hypertrophic signals partly through Akt/GSK3β/β-catenin and Akt/mTOR pathways.

Objective Adipose tissue inflammation plays an important role in the pathogenesis of obesity-associated complications, such as atherosclerosis. Adiponectin secreted from adipocytes has various beneficial effects including anti-inflammatory effect. Obesity often presents with hypoadiponectinemia. However, the mechanism and adiponectin movement in obesity remain uncharacterized. Here we investigated tissue distribution of adiponectin protein in lean and obese mice. Methods Adiponectin protein levels were evaluated by enzyme-linked immunosorbent assay and western blotting. Adipose tissues were fractionated into mature adipocyte fraction (MAF) and stromal vascular fraction (SVF). Results Adiponectin protein was detected not only in MAF but also in SVF, which lacks adiponectin mRNA expression, of adipose tissue remarkably. SVF adiponectin protein level was higher in obese mice than in lean mice. The mechanism of adiponectin accumulation was investigated in adiponectin-deficient (APN-KO) mice after injection of plasma from wild-type mice. These mice showed accumulation of exogenous adiponectin, which derived from wild type mice, in adipose tissues, and the adiponectin was more observed in SVF of diet induced obese APN-KO mice than lean APN-KO mice. Among the adiponectin binding proteins, T-cadherin mRNA and protein levels in SVF of obese mice were remarkably higher than in lean mice. Oxidative stress levels were also significantly higher in SVF of obese mice than lean mice. Mechanistically, H2O2 up-regulated T-cadherin mRNA level in murine macrophages. Conclusions The results demonstrated adiponectin targets to adipose SVF of obese mice. These findings should shed a new light on the pathology of adipose tissue inflammation and hypoadiponectinemia of obesity.

S100A8/A9 complex, calprotectin, which serves as an endogenous ligand for immune pathways, is associated with atherosclerosis. These proteins are reported to have several functions such as activating NADPH oxidase, binding toll-like receptor 4 and associated with the receptor for advanced glycation end-products. We recently reported S100A8 mRNA was highly expressed in mouse white adipose tissues and differentiated 3T3-L1 adipocytes. However, regulation of S100A9 expression in murine adipose tissue remains to be elucidated. The results of our studies in male Japanese, obese and control mice and cultured cells showed: (1) serum levels of S100A8/A9 complex, calprotectin, correlated with visceral fat area, body mass index, subcutaneous fat area, and leukocyte count in 500 Japanese men, and (2) higher mRNA expression levels of S100A8 in mature adipocyte fraction and S100A9 in stromal vascular cell fraction of obese mice, compared with those of lean mice. Overexpression of S100A8 and S100A9 in obese adipose tissue may be involved, at least partly, in not only high circulating levels of S100A8/A9 complex in abdominal obesity but also adipose and systemic tissue inflammation.

Visceral fat adiposity plays an important role in the development of metabolic syndrome. We reported previously the impact of human visceral fat adiposity on gene expression profile of peripheral blood cells. Genes related to circadian rhythm were highly associated with visceral fat area and period homolog 1 (PER1) showed the most significant negative correlation with visceral fat area. However, regulation of adipose Per1 remains poorly understood. The present study was designed to understand the regulation of Per1 in adipose tissues. Adipose Per1 mRNA levels of ob/ob mice were markedly low at 25 and 35 weeks of age. The levels of other core clock genes of white adipose tissues were also low in ob/ob mice at 25 and 35 weeks of age. Per1 mRNA was mainly expressed in the mature adipocyte fraction (MAF) and it was significantly low in MAF of ob/ob mice. To examine the possible mechanisms, 3T3-L1 adipocytes were treated with H2O2, tumor necrosis factor-α (TNF-α), S100A8, and lipopolysaccharide (LPS). However, no significant changes in Per1 mRNA level were observed by these agents. Exposure of cultured 3T3-L1 adipocytes to low temperature (33°C) decreased Per1 and catalase, and increased monocyte chemoattractant protein-1 (Mcp-1) mRNA levels. Hypothermia also worsened insulin-mediated Akt phosphorylation in 3T3-L1 adipocytes. Finally, telemetric analysis showed low temperature of adipose tissues in ob/ob mice. In obesity, adipose hypothermia seems to accelerate adipocyte dysfunction.

Aims Ephrin-B1 (EfnB1) was selected among genes of unknown function in adipocytes or adipose tissue and subjected to thorough analysis to understand its role in the development of obesity. Methods and Results EfnB1 mRNA and protein levels were significantly decreased in adipose tissues of obese mice and such reduction was mainly observed in mature adipocytes. Exposure of 3T3-L1 adipocytes to tumor necrosis factor-α (TNF-α) and their culture with RAW264.7 cells reduced EFNB1 levels. Knockdown of adipose EFNB1 increased monocyte chemoattractant protein-1 (Mcp-1) mRNA level and augmented the TNF-α-mediated THP-1 monocyte adhesion to adipocytes. Adenovirus-mediated adipose EFNB1-overexpression significantly reduced the increase in Mcp-1 mRNA level induced by coculture of 3T3-L1 adipocytes with RAW264.7 cells. Monocyte adherent assay showed that adipose EfnB1-overexpression significantly decreased the increase of monocyte adhesion by coculture with RAW264.7 cells. TNF-α-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) was reduced by EFNB1-overexpression. Conclusions EFNB1 contributes to the suppression of adipose inflammatory response. In obesity, reduction of adipose EFNB1 may accelerate the vicious cycle involved in adipose tissue inflammation.