Project/Area Number |
15081101
|
Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
|
Allocation Type | Single-year Grants |
Review Section |
Biological Sciences
|
Research Institution | Osaka University |
Principal Investigator |
MATSUZAWA Yuji Osaka University, Professor Emeritus (70116101)
|
Co-Investigator(Kenkyū-buntansha) |
FUNAHASHI Tohru Osaka University, Graduate School of Medicine, Associate Professor (60243234)
SAITO Masayuki Hokkaido University, Professor Emeritus (80036441)
YADA Toshihiko Jichi Medical University, School of Medicine, Professor (60166527)
|
Project Period (FY) |
2003 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥41,900,000 (Direct Cost: ¥41,900,000)
Fiscal Year 2007: ¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 2006: ¥8,200,000 (Direct Cost: ¥8,200,000)
Fiscal Year 2005: ¥8,500,000 (Direct Cost: ¥8,500,000)
Fiscal Year 2004: ¥8,500,000 (Direct Cost: ¥8,500,000)
Fiscal Year 2003: ¥8,500,000 (Direct Cost: ¥8,500,000)
|
Keywords | Visceral adipose tissue / Adipocytokine / Adipocyte / Gene expression / Differentiation / 内蔵脂肪 |
Research Abstract |
The aim of this research field is to clarify the functions of adipocyte and adipose tissue to establish an effective strategy for combating lyfe-style-related disorders such as diabetes, atherosclerotic vascular diseases and some types of cancers related to obesity from the clinical observations that many life-style-related disorders are triggered by the accumulation of visceral fat and scientific findings that abnormalities of various adipocyte-derived factors conceptualized as adipocytokines reside a common basis of visceral obesity-related disorders. From three-dimensional analyses of living adipose tissue, coordination of adipogenesis and angiogenesis plays an essential role in the differentiation of adipose tissue in obesity. Rolling and attachment of monocytes were observed in adipose tissue resembling early atherosclerotic vascular changes. Recruited macrophages produced various inflammatory cytokines and affected adipocytokines production, which was conceptualized as adipose tis
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sue remodeling. Local production of oxidative stress and hypoxia also were also proved as underlying possible mechanisms of adipocutokine dysregulation. Adiposome, macrovesicular structure from adipocyte was elucidated as machinery responsible for some kind of adipocytokine secretion. Some types of volume sensing channel were identified as a sensor of adipocyte enlargement and partially responsible for TNF α-induced impairment of glucose uptake. Aquaporin 7, a member of water channel family, was identified as a glycerol channel in adipocyte, and its significance in the body was proved by the fact that the deficiency of this molecule caused profound hypoglycemia in starvation. Vast researches revealed the significance of adiponectin, a defensive molecule derived from adipocyte, and deficiency of adiponectin, hypoadiponectinemia, (which is usually and clinically observed in visceral fat accumulation) plays important roles in the development of disorders in the metabolic syndrome. Idntifycation of AdipoRl and R2, which are possible receptors for adiponectin and precise analyses of mice lacking these molecules confirmed the importance of adiponectin in vivo. We believe that the researches performed in this project really contributed fundamental establishment of a new research field named 'adipomics', which must be required to fight against lyfe-style-related disorders, especially cardiovascular disease explosively prevailing the world Less
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