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Amorfrutins are potent antidiabetic dietary natural products

Item Type:Article
Title:Amorfrutins are potent antidiabetic dietary natural products
Creators Name: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. and Sauer, S.
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.
Keywords:Nuclear Receptors, Nutrition, Compound Screening, Organic Synthesis, X-Ray Structure, Animals, Mice
Source:Proceedings of the National Academy of Sciences of the United States of America
Publisher:National Academy of Sciences
Page Range:7257-7262
Date:8 May 2012
Official Publication:https://doi.org/10.1073/pnas.1116971109
PubMed:View item in PubMed

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