Title:
アジポネクチンの投与により脂肪を減少させるための方法。
Document Type and Number:
Japanese Patent JP2004521930
Kind Code:
A
Abstract:
The stromal cells that support blood cell production within bone marrow are pre-adipocytes and functional interactions with marrow fat cells have long been suspected. Adiponectin was recently isolated as an adipocyte product and shown to have structural similarities to Clq as well as members of the TNF superfamily. It suppresses myeloid differentiation in short term bone marrow cultures and also inhibits macrophage functions. These observations raised the possibility that precursors of other blood cell lineages interact with fat cells in marrow via adiponectin. It has now been determined that the factor blocks B lymphopoiesis in Whitlock-Witte type bone marrow cultures, but not the production of myeloid cells in Dexter cultures. Several observations suggest that non-lymphoid cells represent the target of this new mediator, and the B lymphoid lineage is only indirectly influenced. Highly purified lymphocyte precursors in stromal cell-free, serum-free cultures were unaffected by adiponectin. Similarly, there was no influence on IL-7 responding pro-B cells in clonal assays. However, the cytokine dramatically inhibited adipogenesis in culture, suggesting that it may normally be a feedback inhibitor of this process. PCR analyses revealed that COX-2 is induced on exposure of cloned preadipocytes to adiponectin, resulting in prostaglandin release. This is critical to the inhibition of adipogenesis, because a COX-2 inhibitor, DUP-697 blocked the response of preadipocytes to adiponectin. Furthermore, fat cell formation in response to adiponectin was defective in mice with disruption of the COX-2 gene. In contrast, expression of TNF-alpha, TGF-beta, interferons and a new interferon-like cytokine known as limitin are not up-regulated by adiponectin. These results also demonstrate that COX-2 inducers can be used to cause weight loss, and that COX-2 inhibitors will cause weight gain.
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Inventors:
Kinkade, Paul W.
Yokuta, Takafumi
Yokuta, Takafumi
Application Number:
JP2002571107A
Publication Date:
July 22, 2004
Filing Date:
March 14, 2002
Export Citation:
Assignee:
OKLAHOMA MEDICAL RESEARCH FOUNDATION
International Classes:
A61K38/00; A61K38/17; A61P3/04; A61P43/00; A61K9/00; (IPC1-7): A61K38/00; A61P3/04; A61P43/00
Attorney, Agent or Firm:
Hidesaku Yamamoto
Takaaki Yasumura
Natsuki Morishita
Takaaki Yasumura
Natsuki Morishita