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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., et al. (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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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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 Creators:
Weidner, Christopher1, Author           
de Groot, Jens C.2, Author
Prasad, Aman3, Author
Freiwald, Anja1, Author           
Quedenau, Claudia4, Author           
Kliem, Magdalena1, Author           
Witzke, Annabell1, Author           
Kodelja, Vitam4, Author           
Han, Chung-Ting1, Author           
Giegold, Sascha5, Author
Baumann, Matthias5, Author
Klebl, Bert5, Author
Siems, Karsten6, Author
Müller-Kuhrt, Lutz6, Author
Schürmann, Annette7, Author
Schüler, Rita7, Author
Pfeiffer, Andreas F. H.7, Author
Schroeder, Frank C.3, Author
Büssow, Konrad2, Author
Sauer, Sascha1, Author           
Affiliations:
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              

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 Abstract: 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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Language(s): eng - English
 Dates: 2012-04-162012-05-08
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: PMC: 3358853
DOI: 10.1073/pnas.1116971109
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Title: Proceedings of the National Academy of Sciences of the United States of America
Source Genre: Journal
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Publ. Info: National Academy of Sciences
Pages: 5 Volume / Issue: 109 (19) Sequence Number: - Start / End Page: 7257 - 7262 Identifier: Other: Proc Natl Acad Sci U S A
Other: PNAS
ISSN: 0027-8424
ISSN: 1091-6490