20-Hydroxyecdysone decreases weight and hyperglycemia in a diet-induced obesity mice model.
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.
Kizelsztein
Pablo
P
Rutgers University, 59 Dudley Rd., New Brunswick, NJ 08901, USA. pablok@aesop.rutgers.edu
Govorko
Dmitry
D
Komarnytsky
Slavko
S
Evans
Alysa
A
Wang
Zhong
Z
Cefalu
William T
WT
Raskin
Ilya
I
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052242:Adiponectin / Q000097:blood; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular; D002478:Cells, Cultured; D004041:Dietary Fats / Q000494:pharmacology; D004441:Ecdysterone / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D018149:Glucose Intolerance / Q000188:drug therapy* / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy* / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008113:Liver Neoplasms; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D050794:STAT1 Transcription Factor / Q000187:drug effects
D052242:Adiponectin; C499919:Adipoq protein, mouse; D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D050794:STAT1 Transcription Factor; D004441:Ecdysterone; D019869:Phosphatidylinositol 3-Kinases; D055372:AMP-Activated Protein Kinases