Amorfrutins Are Potent Antidiabetic Dietary Natural Products

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2012 Apr 18

PMID 22509006

Citations 68

Authors

Christopher Weidner

Jens C de Groot

Aman Prasad

Anja Freiwald

Claudia Quedenau

Magdalena Kliem

Annabell Witzke

Vitam Kodelja

Chung-Ting Han

Sascha Giegold

Matthias Baumann

Bert Klebl

Karsten Siems

Lutz Muller-Kuhrt

Annette Schurmann

Rita Schuler

Andreas F H Pfeiffer

Frank C Schroeder

Konrad Bussow

Sascha Sauer

Affiliations

Soon will be listed here.

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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