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  Amorfrutins are potent antidiabetic dietary natural products

Weidner, C., de Groot, J. C., Prasad, A., Freiwald, A., Quedenau, C., Kliem, M., Witzke, A., Kodelja, V., Han, C.-T., Giegold, S., Baumann, M., Klebl, B., Siems, K., Müller-Kuhrt, L., Schürmann, A., Schüler, R., Pfeiffer, A. F. H., Schroeder, F. C., Büssow, K., & Sauer, S. (2012). Amorfrutins are potent antidiabetic dietary natural products. Proceedings of the National Academy of Sciences of the United States of America, 109(19), 7257-7262. doi:10.1073/pnas.1116971109.

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アイテムのパーマリンク: https://hdl.handle.net/11858/00-001M-0000-000E-E4DD-D 版のパーマリンク: https://hdl.handle.net/11858/00-001M-0000-000E-E4DE-B
資料種別: 学術論文

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PNAS-2012-Weidner-1116971109.pdf (出版社版), 2MB
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https://hdl.handle.net/11858/00-001M-0000-000E-E4DC-F
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PNAS-2012-Weidner-1116971109.pdf
説明:
Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease.
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 作成者:
Weidner, Christopher1, 著者           
de Groot, Jens C.2, 著者
Prasad, Aman3, 著者
Freiwald, Anja1, 著者           
Quedenau, Claudia4, 著者           
Kliem, Magdalena1, 著者           
Witzke, Annabell1, 著者           
Kodelja, Vitam4, 著者           
Han, Chung-Ting1, 著者           
Giegold, Sascha5, 著者
Baumann, Matthias5, 著者
Klebl, Bert5, 著者
Siems, Karsten6, 著者
Müller-Kuhrt, Lutz6, 著者
Schürmann, Annette7, 著者
Schüler, Rita7, 著者
Pfeiffer, Andreas F. H.7, 著者
Schroeder, Frank C.3, 著者
Büssow, Konrad2, 著者
Sauer, Sascha1, 著者           
所属:
1Nutrigenomics and Gene Regulation (Sascha Sauer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr. 73, 14195 Berlin, Germany, ou_1479662              
2Division of Structural Biology, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, 38124 Braunschweig, Germany, ou_persistent22              
3Department of Chemistry and Chemical Biology and Boyce Thompson Institute, Cornell University, Ithaca, NY 14853, ou_persistent22              
4Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, Ihnestr. 73, 14195 Berlin, Germany, ou_1433554              
5Lead Discovery Center GmbH, Emil-Figge-Strasse 76a, 44227 Dortmund, Germany, ou_persistent22              
6AnalytiCon Discovery GmbH, Hermannswerder Haus 17, 14473 Potsdam, Germany, ou_persistent22              
7German Institute of Human Nutrition, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany , ou_persistent22              

内容説明

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キーワード: x-ray structure
 要旨: Given worldwide increases in the incidence of obesity and type 2 diabetes, new strategies for preventing and treating metabolic diseases are needed. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a central role in lipid and glucose metabolism; however, current PPARγ-targeting drugs are characterized by undesirable side effects. Natural products from edible biomaterial provide a structurally diverse resource to alleviate complex disorders via tailored nutritional intervention. We identified a family of natural products, the amorfrutins, from edible parts of two legumes, Glycyrrhiza foetida and Amorpha fruticosa, as structurally new and powerful antidiabetics with unprecedented effects for a dietary molecule. Amorfrutins bind to and activate PPARγ, which results in selective gene expression and physiological profiles markedly different from activation by current synthetic PPARγ drugs. In diet-induced obese and db/db mice, amorfrutin treatment strongly improves insulin resistance and other metabolic and inflammatory parameters without concomitant increase of fat storage or other unwanted side effects such as hepatoxicity. These results show that selective PPARγ-activation by diet-derived ligands may constitute a promising approach to combat metabolic disease.

資料詳細

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言語: eng - English
 日付: 2012-04-162012-05-08
 出版の状態: 出版
 ページ: -
 出版情報: -
 目次: -
 査読: 査読あり
 識別子（DOI, ISBNなど）: PMC: 3358853
DOI: 10.1073/pnas.1116971109
 学位: -

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出版物 1

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出版物名: Proceedings of the National Academy of Sciences of the United States of America
種別: 学術雑誌
 著者・編者:
所属:
出版社, 出版地: National Academy of Sciences
ページ: 5 巻号: 109 (19) 通巻号: - 開始・終了ページ: 7257 - 7262 識別子（ISBN, ISSN, DOIなど）: その他: Proc Natl Acad Sci U S A
その他: PNAS
ISSN: 0027-8424
ISSN: 1091-6490