2012 Fiscal Year Final Research Report
In vivo imaging revealed molecular mechanisms of metabolic syndrome and novel biomarkers
| Project/Area Number |
23791016
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Metabolomics
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAGASAKI Mika 東京大学, 医学部附属病院, 特任助教 (70456135)
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| Project Period (FY) |
2011 – 2012
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| Keywords | 共焦点顕微鏡 / メタボリック症候群 / 免疫異常 / リモデ リング / 脂肪組織 |
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| Research Abstract |
To elucidate the underlying mechanisms of metabolic diseases based on chronic inflammation, it is vital to examine the multi-cellular kinetics in living animals. Therefore, we developed in vivo imaging technique based on single- and multi-photon microscopy, and we assessed dynamic immune and inflammatory cellular interplay in diseased conditions. Using this technique, we visualized cell kinetics in metabolic organs including adipose tissue. We also developed FACS analysis methods of metabolic organs, and we identified a novel B cell subset that is abundant in adipose tissue. Adipose B cells also exhibited unique surface phenotypes, distinct from those of known regulatory B cell subsets. Our findings indicate that adipose B cells are a naturally occurring regulatory B cell subset that is essential for negative regulation of diet-induced adipose inflammation and maintenance of homeostasis within adipose tissue, and that B cell dysfunction pivotally contributes to the progression of infla
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mmatory and fibrotic processes.It is known that in obesity adipose tissue expands through both adipocyte hypertrophy and hyperplasia, and that inflammation is induced within visceral adipose tissue. The underlying mechanism that controls these dynamic changes is still not well understood, however. We found that autotaxin (ATX) is an adipose-derived, secreted enzyme that contributes to adipose expansion and inflammation. ATX+/- and adipocyte specific ATX knockout mice fed a high-fat diet exhibited smaller body weight gains than control micefed the same diet. Preadipocytes from ATX+/- mice showed less capacity to proliferate and differentiate into adipocytes than those from ATX+/+ mice. In addition, adipose inflammation was ameliorated by ATX haploinsufficiency. Despite its contribution to adipose obesity, ATX expression was downregulated in obese adipose tissue in mice. Similarly, serum ATX levels were reduced in obese human subjects and were independently correlated with obesity. Taken together, our results establish ATX as an adipose-derived, secreted enzyme that is downregulated in obesity but is centrally involved in mediating adipose obesity. Less
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[Journal Article] In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin signaling2012
Author(s)
Nishimura S, Manabe I, Nagasaki M, Kakuta S, Iwakura Y, Takayama N, Ooehara J, Otsu M, Kamiya A, Petrich B, Urano T, Kadono T, Sato S, Aiba A, Yamashita H, Sugiura S, Kadowaki T, Nakauchi H, Eto K, Nagai R.
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Journal Title
Blood
Volume: 119(8)
Pages: e45-56
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[Presentation] Adipose Natural Regulatory B Cells Negatively Control Adipose Tissue Inflammation Associated with Obesity (Featured Reserach Session)2013
Author(s)
Nisimura S, Nagasaki M, Manabe I, Eto K, Yamashita H, Komuro I, Nagai R Nagasaki M, Nishimura S, Manabe I, Uno K, Yamashita H, Nagai R, Sugita J, Nishimura S, Nagasaki M, Nagai R, Komuro i
Organizer
第77回日本循環器学会学術集会
Place of Presentation
横浜
Year and Date
20130315-17
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