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Am J Physiol Endocrinol Metab 296: E433-E439, 2009. First published January 6, 2009; doi:10.1152/ajpendo.90772.2008
0193-1849/09 $8.00
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20-Hydroxyecdysone decreases weight and hyperglycemia in a diet-induced obesity mice model

Pablo Kizelsztein,1 Dmitry Govorko,1 Slavko Komarnytsky,1 Alysa Evans,1 Zhong Wang,2 William T. Cefalu,2 and Ilya Raskin1

1Biotech Center, Rutgers University, New Brunswick, New Jersey; and 2Pennington Biomedical Research Center, Baton Rouge, Louisiana

Submitted 17 September 2008 ; accepted in final form 30 December 2008

The steroid hormone 20-hydroxyecdysone (20HE) is an essential signaling molecule that modulates molting response in insects and may function as a putative anabolic factor in vertebrate animals, although no mammalian 20HE receptor has been identified. Here we show that in H4IIE cell culture, 20HE treatment decreased expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase), reduced glucose production, and induced Akt2 phosphorylation sensitive to the phosphoinositide-3 kinase pathway-specific inhibitor LY-294002. Daily oral administration of 20HE (10 mg/kg for 13 wk) ameliorated obesity and insulin resistance in C57BL/6J mice fed a high-fat diet and produced a significant decrease of body weight gain and body fat mass compared with nontreated animals as demonstrated by dual-energy X-ray absorptiometry analysis. In addition, plasma insulin levels and glucose tolerance were significantly lowered by 20HE treatment. These changes were accompanied by the reduced hepatic expression of PEPCK and G6Pase and increased adiponectin production by visceral fat tissue. These studies demonstrate the anti-obesity and anti-diabetic effects of 20HE and begin to elucidate its putative cellular targets both in vitro and in vivo.

gluconeogenic enzymes; adiponectin; obesity and diabetes



Address for reprint requests and other correspondence: P. Kizelsztein, Biotech Center, Rutgers University, 59 Dudley Rd., New Brunswick, NJ 08901 (e-mail: pablok{at}aesop.rutgers.edu)







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