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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Han, Chung-ting Klebl, Bert Prasad, Aman Büssow, Konrad Pfeiffer, Andreas F. H. Schroeder, Frank C. Siems, Karsten Weidner, Christopher Giegold, Sascha Baumann, Matthias Schüler, Rita Freiwald, Anja Sauer, Sascha De Groot, Jens C. Quedenau, Claudia Witzke, Annabell Kliem, Magdalena Schürmann, Annette Kodelja, Vitam Müller-kuhrt, Lutz |
| Description | Author Affiliation: Weidner C ( Otto Warburg Laboratory, Max Planck Institute for Molecular Genetics, Ihnestrasse 63-73, 14195 Berlin, Germany.); |
| 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 19 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-05-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Biological Products Pharmacology Diabetes Mellitus, Type 2 Drug Therapy Fabaceae Chemistry Hypoglycemic Agents Salicylates 3T3-L1 Cells Animals Metabolism Blotting, Western CHO Cells Cricetinae Cricetulus Crystallography, X-Ray Complications Etiology Diet, High-Fat Adverse Effects Dietary Supplements Gene Expression Drug Effects Glycyrrhiza Mice Mice, Inbred C57BL Molecular Structure Obesity PPAR Gamma Genetics Protein Binding Reverse Transcriptase Polymerase Chain Reaction Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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