We explored the possibility that brown rice-specific bioactive substances, γ-oryzanol would modulate the function of brain reward system in mice. In striatum from mice fed high fat diet, expression of type 2 dopamine receptor (D2R) was decreased via the increase in DNA methylation of its promoter region. Co-administration of γ-oryzanol decreased the expression and activity of DNA methyltransferases (DNMTs), thereby restoring the expression of D2R in striatum. Pharmacological inhibition of DNMTs by 5-aza-2'-deoxycytidine also ameliorated preference for dietary fat. Consistent with these findings, enzymatic in vitro assays demonstrated that γ-oryzanol inhibited the activity of DNMTs. We demonstrated that γ-oryzanol ameliorates HFD-induced DNA hypermethylation of the promoter region of D2R in striatum in mice. Our experimental paradigm highlights γ-oryzanol as a promising anti-obesity as well as anti-diabetic substance with a distinct property of novel epigenetic modulator.

We explored the possibility that brown rice-specific bioactive substances, γ-oryzanol would modulate the function of brain reward system in mice. In striatum from mice fed high fat diet, expression of type 2 dopamine receptor (D2R) was decreased via the increase in DNA methylation of its promoter region. Co-administration of γ-oryzanol decreased the expression and activity of DNA methyltransferases (DNMTs), thereby restoring the expression of D2R in striatum. Pharmacological inhibition of DNMTs by 5-aza-2'-deoxycytidine also ameliorated preference for dietary fat. Consistent with these findings, enzymatic in vitro assays demonstrated that γ-oryzanol inhibited the activity of DNMTs. We demonstrated that γ-oryzanol ameliorates HFD-induced DNA hypermethylation of the promoter region of D2R in striatum in mice. Our experimental paradigm highlights γ-oryzanol as a promising anti-obesity as well as anti-diabetic substance with a distinct property of novel epigenetic modulator.

We explored the possibility that brown rice-specific bioactive substances, γ-oryzanol would modulate the function of brain reward system in mice. In striatum from mice fed high fat diet, expression of type 2 dopamine receptor (D2R) was decreased via the increase in DNA methylation of its promoter region. Co-administration of γ-oryzanol decreased the expression and activity of DNA methyltransferases (DNMTs), thereby restoring the expression of D2R in striatum. Pharmacological inhibition of DNMTs by 5-aza-2'-deoxycytidine also ameliorated preference for dietary fat. Consistent with these findings, enzymatic in vitro assays demonstrated that γ-oryzanol inhibited the activity of DNMTs. We demonstrated that γ-oryzanol ameliorates HFD-induced DNA hypermethylation of the promoter region of D2R in striatum in mice. Our experimental paradigm highlights γ-oryzanol as a promising anti-obesity as well as anti-diabetic substance with a distinct property of novel epigenetic modulator.

We explored the possibility that brown rice-specific bioactive substances, γ-oryzanol would modulate the function of brain reward system in mice. In striatum from mice fed high fat diet, expression of type 2 dopamine receptor (D2R) was decreased via the increase in DNA methylation of its promoter region. Co-administration of γ-oryzanol decreased the expression and activity of DNA methyltransferases (DNMTs), thereby restoring the expression of D2R in striatum. Pharmacological inhibition of DNMTs by 5-aza-2'-deoxycytidine also ameliorated preference for dietary fat. Consistent with these findings, enzymatic in vitro assays demonstrated that γ-oryzanol inhibited the activity of DNMTs. We demonstrated that γ-oryzanol ameliorates HFD-induced DNA hypermethylation of the promoter region of D2R in striatum in mice. Our experimental paradigm highlights γ-oryzanol as a promising anti-obesity as well as anti-diabetic substance with a distinct property of novel epigenetic modulator.

Infusion reaction is a side effect that occurs immediately after antibody drug administration, and its prediction is becoming very important. In this study, we identified infusion reaction risk factors by analyzing genetic polymorphisms in patients who developed adverse effects immediately after rituximab administration. [Significance] By identifying risk factors such as the effects of FcRn genetic polymorphism, it is expected that the optimal use of rituximab can be considered taking into consideration individual differences in their genetic polymorphism. [Importance] It is expected that this study may be generalized to antibody drugs and could be applied to "preclinical tests" performed prior to clinical trials where antibody drugs are first administered to humans.

Infusion reaction is a side effect that occurs immediately after antibody drug administration, and its prediction is becoming very important. In this study, we identified infusion reaction risk factors by analyzing genetic polymorphisms in patients who developed adverse effects immediately after rituximab administration. [Significance] By identifying risk factors such as the effects of FcRn genetic polymorphism, it is expected that the optimal use of rituximab can be considered taking into consideration individual differences in their genetic polymorphism. [Importance] It is expected that this study may be generalized to antibody drugs and could be applied to "preclinical tests" performed prior to clinical trials where antibody drugs are first administered to humans.

Infusion reaction is a side effect that occurs immediately after antibody drug administration, and its prediction is becoming very important. In this study, we identified infusion reaction risk factors by analyzing genetic polymorphisms in patients who developed adverse effects immediately after rituximab administration. [Significance] By identifying risk factors such as the effects of FcRn genetic polymorphism, it is expected that the optimal use of rituximab can be considered taking into consideration individual differences in their genetic polymorphism. [Importance] It is expected that this study may be generalized to antibody drugs and could be applied to "preclinical tests" performed prior to clinical trials where antibody drugs are first administered to humans.

Infusion reaction is a side effect that occurs immediately after antibody drug administration, and its prediction is becoming very important. In this study, we identified infusion reaction risk factors by analyzing genetic polymorphisms in patients who developed adverse effects immediately after rituximab administration. [Significance] By identifying risk factors such as the effects of FcRn genetic polymorphism, it is expected that the optimal use of rituximab can be considered taking into consideration individual differences in their genetic polymorphism. [Importance] It is expected that this study may be generalized to antibody drugs and could be applied to "preclinical tests" performed prior to clinical trials where antibody drugs are first administered to humans.

We developed a mice animal model of undernourishment in utero deteriorating hepatic steatosis in adult period. Using this animal model, we demonstrated that undernourishment in utero programs the augmentation of endoplasmic reticulum stress in the lever in response to obesogenic diet in adult period, causatively associated with the deterioration of hepatic steatosis and choronic inflammation. The alleviation of ER stress with the treatment of chemical chaperone, tauroursodeoxycholic acid (TUDCA), markedly improved both hepatic steatosis and chronic inflammation. The alleviation of ER stress would be a promising strategy of preemptive medicine against developmental origins of hepatic steatosis.

We developed a mice animal model of undernourishment in utero deteriorating hepatic steatosis in adult period. Using this animal model, we demonstrated that undernourishment in utero programs the augmentation of endoplasmic reticulum stress in the lever in response to obesogenic diet in adult period, causatively associated with the deterioration of hepatic steatosis and choronic inflammation. The alleviation of ER stress with the treatment of chemical chaperone, tauroursodeoxycholic acid (TUDCA), markedly improved both hepatic steatosis and chronic inflammation. The alleviation of ER stress would be a promising strategy of preemptive medicine against developmental origins of hepatic steatosis.

We developed a mice animal model of undernourishment in utero deteriorating hepatic steatosis in adult period. Using this animal model, we demonstrated that undernourishment in utero programs the augmentation of endoplasmic reticulum stress in the lever in response to obesogenic diet in adult period, causatively associated with the deterioration of hepatic steatosis and choronic inflammation. The alleviation of ER stress with the treatment of chemical chaperone, tauroursodeoxycholic acid (TUDCA), markedly improved both hepatic steatosis and chronic inflammation. The alleviation of ER stress would be a promising strategy of preemptive medicine against developmental origins of hepatic steatosis.

We developed a mice animal model of undernourishment in utero deteriorating hepatic steatosis in adult period. Using this animal model, we demonstrated that undernourishment in utero programs the augmentation of endoplasmic reticulum stress in the lever in response to obesogenic diet in adult period, causatively associated with the deterioration of hepatic steatosis and choronic inflammation. The alleviation of ER stress with the treatment of chemical chaperone, tauroursodeoxycholic acid (TUDCA), markedly improved both hepatic steatosis and chronic inflammation. The alleviation of ER stress would be a promising strategy of preemptive medicine against developmental origins of hepatic steatosis.

11β-HSD1, which converts inactive cortisone to active cortisol intracellularly, has been reported to play a pivotal role in metabolic diseases as well as chronic inflammatory diseases. However, the involvement of 11β-HSD1 in chronic periodontitis has not been investigated. In this study the relationship between chronic periodontitis, the levels of 11β-HSD1 mRNA, and obesity was examined. The expression of 11β-HSD1 mRNA was significantly higher in the chronic periodontitis group than in the controls. Since the expression of 11β-HSD2 mRNA, which inactivates cortisol, was slightly lower in the periodontitis group than in the controls, the ratio of 11β-HSD1 versus 11β-HSD2 mRNA was still higher in the former than in the latter. However, a correlation was not observed between the levels of 11β-HSD1 mRNA and body mass index, an index of obesity. These results suggest that the increased 11β-HSD1 may play a role in the pathology of chronic periodontitis irrespective of obesity.

11β-HSD1, which converts inactive cortisone to active cortisol intracellularly, has been reported to play a pivotal role in metabolic diseases as well as chronic inflammatory diseases. However, the involvement of 11β-HSD1 in chronic periodontitis has not been investigated. In this study the relationship between chronic periodontitis, the levels of 11β-HSD1 mRNA, and obesity was examined. The expression of 11β-HSD1 mRNA was significantly higher in the chronic periodontitis group than in the controls. Since the expression of 11β-HSD2 mRNA, which inactivates cortisol, was slightly lower in the periodontitis group than in the controls, the ratio of 11β-HSD1 versus 11β-HSD2 mRNA was still higher in the former than in the latter. However, a correlation was not observed between the levels of 11β-HSD1 mRNA and body mass index, an index of obesity. These results suggest that the increased 11β-HSD1 may play a role in the pathology of chronic periodontitis irrespective of obesity.

11β-HSD1, which converts inactive cortisone to active cortisol intracellularly, has been reported to play a pivotal role in metabolic diseases as well as chronic inflammatory diseases. However, the involvement of 11β-HSD1 in chronic periodontitis has not been investigated. In this study the relationship between chronic periodontitis, the levels of 11β-HSD1 mRNA, and obesity was examined. The expression of 11β-HSD1 mRNA was significantly higher in the chronic periodontitis group than in the controls. Since the expression of 11β-HSD2 mRNA, which inactivates cortisol, was slightly lower in the periodontitis group than in the controls, the ratio of 11β-HSD1 versus 11β-HSD2 mRNA was still higher in the former than in the latter. However, a correlation was not observed between the levels of 11β-HSD1 mRNA and body mass index, an index of obesity. These results suggest that the increased 11β-HSD1 may play a role in the pathology of chronic periodontitis irrespective of obesity.

The aim of the study was to verify the effectiveness of continuous glucose monitoring system (CGMS) for self-control in type 2 diabetics. Semi-structured interviews were also conducted to six patients with type 2 diabetes used CGMS for a week, and the interview data were analyzed using a grounded theory approach. Graphical presentation of continuous glucose levels led patients to come to realize their unbalanced diets. This awareness motivated them to improve their eating habits. The Problem Areas in Diabetes (PAID) survey was conducted before and after 20 adult patients used a CGMS. The Student's t-test were used to analyze associations between the PAID score and background factors of patients. PAID scores showed a significant association with patient employment status in terms of reducing the emotional burden due to the treatment of diabetes (p<0.05). These researches suggest that CGMS is effective in patient motivation and educating people with jobs about diabetes.

11β-HSD1, which converts inactive cortisone to active cortisol intracellularly, has been reported to play a pivotal role in metabolic diseases as well as chronic inflammatory diseases. However, the involvement of 11β-HSD1 in chronic periodontitis has not been investigated. In this study the relationship between chronic periodontitis, the levels of 11β-HSD1 mRNA, and obesity was examined. The expression of 11β-HSD1 mRNA was significantly higher in the chronic periodontitis group than in the controls. Since the expression of 11β-HSD2 mRNA, which inactivates cortisol, was slightly lower in the periodontitis group than in the controls, the ratio of 11β-HSD1 versus 11β-HSD2 mRNA was still higher in the former than in the latter. However, a correlation was not observed between the levels of 11β-HSD1 mRNA and body mass index, an index of obesity. These results suggest that the increased 11β-HSD1 may play a role in the pathology of chronic periodontitis irrespective of obesity.

The aim of the study was to verify the effectiveness of continuous glucose monitoring system (CGMS) for self-control in type 2 diabetics. Semi-structured interviews were also conducted to six patients with type 2 diabetes used CGMS for a week, and the interview data were analyzed using a grounded theory approach. Graphical presentation of continuous glucose levels led patients to come to realize their unbalanced diets. This awareness motivated them to improve their eating habits. The Problem Areas in Diabetes (PAID) survey was conducted before and after 20 adult patients used a CGMS. The Student's t-test were used to analyze associations between the PAID score and background factors of patients. PAID scores showed a significant association with patient employment status in terms of reducing the emotional burden due to the treatment of diabetes (p<0.05). These researches suggest that CGMS is effective in patient motivation and educating people with jobs about diabetes.

11β-HSD1, which converts inactive cortisone to active cortisol intracellularly, has been reported to play a pivotal role in metabolic diseases as well as chronic inflammatory diseases. However, the involvement of 11β-HSD1 in chronic periodontitis has not been investigated. In this study the relationship between chronic periodontitis, the levels of 11β-HSD1 mRNA, and obesity was examined. The expression of 11β-HSD1 mRNA was significantly higher in the chronic periodontitis group than in the controls. Since the expression of 11β-HSD2 mRNA, which inactivates cortisol, was slightly lower in the periodontitis group than in the controls, the ratio of 11β-HSD1 versus 11β-HSD2 mRNA was still higher in the former than in the latter. However, a correlation was not observed between the levels of 11β-HSD1 mRNA and body mass index, an index of obesity. These results suggest that the increased 11β-HSD1 may play a role in the pathology of chronic periodontitis irrespective of obesity.

Vascular endothelial dysfunction is an early marker for atherosclerosis. We investigated the effect of metabolic stress on vascular endothelial function in human and/or experimental animas. We found brown rice improve vascular endothelial function of metabolic syndrome subjects compared to white rice as well as their insulin sensitivity. Gamma-oryzanol, a major content of brown rice, improve glucose metabolism, reduce hypothalamic ER stress, and, consequently, attenuate the preference for dietary fat in mice. Xanthine oxidase is one of major source of reactive oxygen species in metabolic syndrome subjects. We reported that inhibition of xanthine oxidase reduces oxidative stress and improves vascular endothelial dysfunction in metabolic stress mouse. Xanthine oxidase inhibitor, such as allopurinol and febuxostat may be effective to suppress progression of atherosclerosis.

The present study demonstrated for the first time in mouse experiments that excess intake of fatty foods augments ER stress in hypothalamus, which in turn increases the preference for dietary fats, thereby making a self-adjusting circuit. Gamma-oryzanol is a unique bioactive substance exclusively and abundantly found in brown rice. We found that γ-oryzanol decreases ER stress in hypothalamus and attenuates the preference for dietary fat, thereby ameliorating high fat diet (HFD)-induced fuel dyshomeostasis. We also tested whether γ-oryzanol reduces ER stress and improves function and survival of pancreatic β-cells under high fat diet in mice. In pancreatic islets from HFD-fed diabetic mice, oral administration of γ-oryzanol improved glucose stimulated insulin secretion (GSIS) on following reduction of exaggerated ER stress and apoptosis. A line of novel findings may open a fresh avenue for natural food-based approach toward the prevention of obesity-diabetes syndrome.

Vascular endothelial dysfunction is an early marker for atherosclerosis. We investigated the effect of metabolic stress on vascular endothelial function in human and/or experimental animas. We found brown rice improve vascular endothelial function of metabolic syndrome subjects compared to white rice as well as their insulin sensitivity. Gamma-oryzanol, a major content of brown rice, improve glucose metabolism, reduce hypothalamic ER stress, and, consequently, attenuate the preference for dietary fat in mice. Xanthine oxidase is one of major source of reactive oxygen species in metabolic syndrome subjects. We reported that inhibition of xanthine oxidase reduces oxidative stress and improves vascular endothelial dysfunction in metabolic stress mouse. Xanthine oxidase inhibitor, such as allopurinol and febuxostat may be effective to suppress progression of atherosclerosis.

The present study demonstrated for the first time in mouse experiments that excess intake of fatty foods augments ER stress in hypothalamus, which in turn increases the preference for dietary fats, thereby making a self-adjusting circuit. Gamma-oryzanol is a unique bioactive substance exclusively and abundantly found in brown rice. We found that γ-oryzanol decreases ER stress in hypothalamus and attenuates the preference for dietary fat, thereby ameliorating high fat diet (HFD)-induced fuel dyshomeostasis. We also tested whether γ-oryzanol reduces ER stress and improves function and survival of pancreatic β-cells under high fat diet in mice. In pancreatic islets from HFD-fed diabetic mice, oral administration of γ-oryzanol improved glucose stimulated insulin secretion (GSIS) on following reduction of exaggerated ER stress and apoptosis. A line of novel findings may open a fresh avenue for natural food-based approach toward the prevention of obesity-diabetes syndrome.

Vascular endothelial dysfunction is an early marker for atherosclerosis. We investigated the effect of metabolic stress on vascular endothelial function in human and/or experimental animas. We found brown rice improve vascular endothelial function of metabolic syndrome subjects compared to white rice as well as their insulin sensitivity. Gamma-oryzanol, a major content of brown rice, improve glucose metabolism, reduce hypothalamic ER stress, and, consequently, attenuate the preference for dietary fat in mice. Xanthine oxidase is one of major source of reactive oxygen species in metabolic syndrome subjects. We reported that inhibition of xanthine oxidase reduces oxidative stress and improves vascular endothelial dysfunction in metabolic stress mouse. Xanthine oxidase inhibitor, such as allopurinol and febuxostat may be effective to suppress progression of atherosclerosis.

The present study demonstrated for the first time in mouse experiments that excess intake of fatty foods augments ER stress in hypothalamus, which in turn increases the preference for dietary fats, thereby making a self-adjusting circuit. Gamma-oryzanol is a unique bioactive substance exclusively and abundantly found in brown rice. We found that γ-oryzanol decreases ER stress in hypothalamus and attenuates the preference for dietary fat, thereby ameliorating high fat diet (HFD)-induced fuel dyshomeostasis. We also tested whether γ-oryzanol reduces ER stress and improves function and survival of pancreatic β-cells under high fat diet in mice. In pancreatic islets from HFD-fed diabetic mice, oral administration of γ-oryzanol improved glucose stimulated insulin secretion (GSIS) on following reduction of exaggerated ER stress and apoptosis. A line of novel findings may open a fresh avenue for natural food-based approach toward the prevention of obesity-diabetes syndrome.

Vascular endothelial dysfunction is an early marker for atherosclerosis. We investigated the effect of metabolic stress on vascular endothelial function in human and/or experimental animas. We found brown rice improve vascular endothelial function of metabolic syndrome subjects compared to white rice as well as their insulin sensitivity. Gamma-oryzanol, a major content of brown rice, improve glucose metabolism, reduce hypothalamic ER stress, and, consequently, attenuate the preference for dietary fat in mice. Xanthine oxidase is one of major source of reactive oxygen species in metabolic syndrome subjects. We reported that inhibition of xanthine oxidase reduces oxidative stress and improves vascular endothelial dysfunction in metabolic stress mouse. Xanthine oxidase inhibitor, such as allopurinol and febuxostat may be effective to suppress progression of atherosclerosis.

The present study demonstrated for the first time in mouse experiments that excess intake of fatty foods augments ER stress in hypothalamus, which in turn increases the preference for dietary fats, thereby making a self-adjusting circuit. Gamma-oryzanol is a unique bioactive substance exclusively and abundantly found in brown rice. We found that γ-oryzanol decreases ER stress in hypothalamus and attenuates the preference for dietary fat, thereby ameliorating high fat diet (HFD)-induced fuel dyshomeostasis. We also tested whether γ-oryzanol reduces ER stress and improves function and survival of pancreatic β-cells under high fat diet in mice. In pancreatic islets from HFD-fed diabetic mice, oral administration of γ-oryzanol improved glucose stimulated insulin secretion (GSIS) on following reduction of exaggerated ER stress and apoptosis. A line of novel findings may open a fresh avenue for natural food-based approach toward the prevention of obesity-diabetes syndrome.

Prospective cohort study showed that average energy intake in Japanese pregnant women in Hamamatsu City was slightly less than 1,600 k cal/day, being much lower than the governmental recommendation. Therefore, considerable numbers of fetuses are supposed to be undernourished. By using a mice animal model of undernourishment in utero, we demonstrated the “Catch-Up-Related Adipose Tissue Remodeling Hypothesis ", that is rapid catch-up growth subsequent to undernourishment in utero may induce chronic inflammation and remodeling in adipose tissue in later life and be causatively associated with the development of metabolic syndrome.