Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
AJP: Endocrinology and Metabolism
Year: 2010  |  Volume: 298  |  Issue: 4  |  Page No.: 787 - 798

PDK-1/FoxO1 pathway in POMC neurons regulates Pomc expression and food intake

K Iskandar, Y Cao, Y Hayashi, M Nakata, E Takano, T Yada, C Zhang, W Ogawa, M Oki, S Chua, H Itoh, T Noda, M Kasuga and J. Nakae    

Abstract:

Both insulin and leptin signaling converge on phosphatidylinositol 3-OH kinase [PI(3)K]/3-phosphoinositide-dependent protein kinase-1 (PDK-1)/protein kinase B (PKB, also known as Akt) in proopiomelanocortin (POMC) neurons. Forkhead box-containing protein-O1 (FoxO1) is inactivated in a PI(3)K-dependent manner. However, the interrelationship between PI(3)K/PDK-1/Akt and FoxO1, and the chronic effects of the overexpression of FoxO1 in POMC neurons on energy homeostasis has not been elucidated. To determine the extent to which PDK-1 and FoxO1 signaling in POMC neurons was responsible for energy homeostasis, we generated POMC neuron-specific Pdk1 knockout mice (POMCPdk1–/–) and mice selectively expressing a constitutively nuclear (CN)FoxO1 or transactivation-defective (256)FoxO1 in POMC neurons (CNFoxO1POMC or 256FoxO1POMC). POMCPdk1–/– mice showed increased food intake and body weight accompanied by decreased expression of Pomc gene. The CNFoxO1POMC mice exhibited mild obesity and hyperphagia compared with POMCPdk1–/– mice. Although expression of the CNFoxO1 made POMCPdk1–/– mice more obese due to excessive suppression of Pomc gene, overexpression of 256FoxO1 in POMC neurons had no effects on metabolic phenotypes and Pomc expression levels of POMCPdk1–/– mice. These data suggest a requirement for PDK-1 and FoxO1 in transcriptional regulation of Pomc and food intake.

View Fulltext    |   Related Articles   |   Back
   
 
 
 
  Related Articles

No Article Found
 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility