Grant-in-Aid for Scientific Research -

Application of 11beta-HSD1 inhibitors to the treatment of periodontal disease

Grant-in-Aid for Scientific Research(C)

Project Year: 2013.04  -  2016.03 

Investigator(s): SAWAI Hirofumi, MASUZAKI Hiroaki, UMEDA Makoto 

Direct: 3,600,000 (YEN)  Overheads: 4,680,000 (YEN)  Total: 1,080,000 (YEN)

　View Summary

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.

mechanisms of vascular endothelial function in metabolic syndrome subjects and novel therapeutic approach

Grant-in-Aid for Scientific Research(C)

Project Year: 2012.04  -  2015.03 

Investigator(s): YAMAKAWA Ken, HIGA Moritake, SHIMABUKURO Michio, MASUZAKI Hiroaki 

Direct: 4,000,000 (YEN)  Overheads: 5,200,000 (YEN)  Total: 1,200,000 (YEN)

　View Summary

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.

Exploration of novel hypothalamic mechanism on fatty food preference and its application to clinical science on obesity-diabetes syndrome

Grant-in-Aid for Scientific Research(C)

Project Year: 2012.04  -  2015.03 

Investigator(s): MASUZAKI Hiroaki, TAKAYAMA Chitoshi, SHIMABUKURO Michio, MATUSHITA Masayuki, KOZUKA Chisayo 

Direct: 4,000,000 (YEN)  Overheads: 5,200,000 (YEN)  Total: 1,200,000 (YEN)

　View Summary

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.

mechanisms of vascular endothelial function in metabolic syndrome subjects and novel therapeutic approach

Grant-in-Aid for Scientific Research(C)

Project Year: 2012.04  -  2015.03 

Investigator(s): YAMAKAWA Ken, HIGA Moritake, SHIMABUKURO Michio, MASUZAKI Hiroaki 

Direct: 4,000,000 (YEN)  Overheads: 5,200,000 (YEN)  Total: 1,200,000 (YEN)

　View Summary

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.

Exploration of novel hypothalamic mechanism on fatty food preference and its application to clinical science on obesity-diabetes syndrome

Grant-in-Aid for Scientific Research(C)

Project Year: 2012.04  -  2015.03 

Investigator(s): MASUZAKI Hiroaki, TAKAYAMA Chitoshi, SHIMABUKURO Michio, MATUSHITA Masayuki, KOZUKA Chisayo 

Direct: 4,000,000 (YEN)  Overheads: 5,200,000 (YEN)  Total: 1,200,000 (YEN)

　View Summary

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.

mechanisms of vascular endothelial function in metabolic syndrome subjects and novel therapeutic approach

Grant-in-Aid for Scientific Research(C)

Project Year: 2012.04  -  2015.03 

Investigator(s): YAMAKAWA Ken, HIGA Moritake, SHIMABUKURO Michio, MASUZAKI Hiroaki 

Direct: 4,000,000 (YEN)  Overheads: 5,200,000 (YEN)  Total: 1,200,000 (YEN)

　View Summary

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.

Exploration of novel hypothalamic mechanism on fatty food preference and its application to clinical science on obesity-diabetes syndrome

Grant-in-Aid for Scientific Research(C)

Project Year: 2012.04  -  2015.03 

Investigator(s): MASUZAKI Hiroaki, TAKAYAMA Chitoshi, SHIMABUKURO Michio, MATUSHITA Masayuki, KOZUKA Chisayo 

Direct: 4,000,000 (YEN)  Overheads: 5,200,000 (YEN)  Total: 1,200,000 (YEN)

　View Summary

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.

mechanisms of vascular endothelial function in metabolic syndrome subjects and novel therapeutic approach

Grant-in-Aid for Scientific Research(C)

Project Year: 2012.04  -  2015.03 

Investigator(s): YAMAKAWA Ken, HIGA Moritake, SHIMABUKURO Michio, MASUZAKI Hiroaki 

Direct: 4,000,000 (YEN)  Overheads: 5,200,000 (YEN)  Total: 1,200,000 (YEN)

　View Summary

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.

Exploration of novel hypothalamic mechanism on fatty food preference and its application to clinical science on obesity-diabetes syndrome

Grant-in-Aid for Scientific Research(C)

Project Year: 2012.04  -  2015.03 

Investigator(s): MASUZAKI Hiroaki, TAKAYAMA Chitoshi, SHIMABUKURO Michio, MATUSHITA Masayuki, KOZUKA Chisayo 

Direct: 4,000,000 (YEN)  Overheads: 5,200,000 (YEN)  Total: 1,200,000 (YEN)

　View Summary

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.

Rapid catch-up growth subsequent to undernourishment in utero and metabolic syndrome in later life

Grant-in-Aid for Scientific Research(B)

Project Year: 2012.04  -  2015.03 

Investigator(s): ITOH Hiroaki, SUGIHARA Kazuhiro, SUZUKI Kazunao, OGAWA Yoshihiro, MASUZAKI Hiroaki, TUCHIYA Knji, MATSUZAKI Hideo, UDAGAWA Jun 

Direct: 13,900,000 (YEN)  Overheads: 18,070,000 (YEN)  Total: 4,170,000 (YEN)

　View Summary

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.

Grant-in-Aid for Scientific Research(C)

Project Year: 2012  -  2014 

Grant-in-Aid for Scientific Research(C)

Project Year: 2012  -  2014 

Grant-in-Aid for Scientific Research(C)

Project Year: 2011  -  2013 

Grant-in-Aid for Scientific Research(C)

Project Year: 2010  -  2012 

Grant-in-Aid for Scientific Research(C)

Project Year: 2010  -  2012 

Grant-in-Aid for Scientific Research(B)

Project Year: 2009  -  2011 

Grant-in-Aid for Scientific Research(B)

Project Year: 2009  -  2009 

Direct: 4,700,000 (YEN)  Overheads: 1,410,000 (YEN)  Total: 6,110,000 (YEN)

Grant-in-Aid for Scientific Research(B)

Project Year: 2006  -  2007 

Grant-in-Aid for Scientific Research(B)

Project Year: 2005  -  2006 

Grant-in-Aid for Scientific Research(S)

Project Year: 2004  -  2008