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Journal Article

Amorfrutins are potent antidiabetic dietary natural products

MPS-Authors
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Weidner,  Christopher
Nutrigenomics and Gene Regulation (Sascha Sauer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Freiwald,  Anja
Nutrigenomics and Gene Regulation (Sascha Sauer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Quedenau,  Claudia
Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Kliem,  Magdalena
Nutrigenomics and Gene Regulation (Sascha Sauer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Witzke,  Annabell
Nutrigenomics and Gene Regulation (Sascha Sauer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Kodelja,  Vitam
Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Han,  Chung-Ting
Nutrigenomics and Gene Regulation (Sascha Sauer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Sauer,  Sascha
Nutrigenomics and Gene Regulation (Sascha Sauer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society;

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PNAS-2012-Weidner-1116971109.pdf
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Citation

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.


Cite as: https://hdl.handle.net/11858/00-001M-0000-000E-E4DD-D
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.