Amorfrutins are selective PPARγ agonists with potent antidiabetic properties

Faced by an alarming incidence of metabolic diseases including obesity and type 2 diabetes worldwide, there is an urgent need for effective strategies for preventing and treating these common diseases. The nuclear receptor PPARγ (peroxisome proliferator-activated receptor gamma) plays a crucial role in metabolism. We isolated the amorfrutins from edible parts of the plants Glychyrrhiza foetida and Amorpha fruticosa, and identified these natural products as a new chemical class to treat insulin resistance and diabetes by selectively activating PPARγ. In contrast to existing synthetic PPARγ drugs, the amorfrutins display unique properties by separating insulin sensitization from unwanted side effects. In obese mouse models, amorfrutin treatment significantly improved important metabolic and inflammatory parameters. In summary, PPARγ activation by selective amorfrutins derived from edible biomaterial is a promising approach to combat metabolic diseases and other diseases in which PPARγ is involved in. GSM701612-GSM701623: Male DIO C57BL/6 mice (age 18 wks), 3 groups (n=4 each after pooling of 8 samples per group). Mice were fed over 3 wks with high fat diet (HFD) without compound (vehicle), HFD with 4 mg/kg/d rosiglitazone or with 100 mg/kg/d amorfrutin 1. Liver RNA extracted. --> 4 biological replicates, vehicle vs. rosiglitazone or amorfrutin 1 GSM702299-GSM702344: Biological replicates (n = 3-4 each) of human primary adipocytes were treated with the following compounds for 24 hours. 10µM rosiglitazone, 10µM pioglitazone, 30µM telmisartan, 10µM nTZDpa, 30µM amorfrutin 1, 30µM amorfrutin 2, 30µM amorfrutin 3 or 30µM amorfrutin 4 vs. 0.1% DMSO (vehicle)