| First Author | Cao Y | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 4 | Pages | e18324 |
| PubMed ID | 21694754 | Mgi Jnum | J:274061 |
| Mgi Id | MGI:6221001 | Doi | 10.1371/journal.pone.0018324 |
| Citation | Cao Y, et al. (2011) PDK1-Foxo1 in agouti-related peptide neurons regulates energy homeostasis by modulating food intake and energy expenditure. PLoS One 6(4):e18324 |
| abstractText | Insulin and leptin intracellular signaling pathways converge and act synergistically on the hypothalamic phosphatidylinositol-3-OH kinase/3-phosphoinositide-dependent protein kinase 1 (PDK1). However, little is known about whether PDK1 in agouti-related peptide (AGRP) neurons contributes to energy homeostasis. We generated AGRP neuron-specific PDK1 knockout (AGRPPdk1(-/-)) mice and mice with selective expression of transactivation-defective Foxo1 (Delta256Foxo1(AGRP)Pdk1(-/-)). The AGRPPdk1(-/-) mice showed reductions in food intake, body length, and body weight. The Delta256Foxo1(AGRP)Pdk1(-/-) mice showed increased body weight, food intake, and reduced locomotor activity. After four weeks of calorie-restricted feeding, oxygen consumption and locomotor activity were elevated in AGRPPdk1(-/-) mice and reduced in Delta256Foxo1(AGRP)Pdk1(-/-) mice. In vitro, ghrelin-induced changes in [Ca(2+)](i) and inhibition of ghrelin by leptin were significantly attenuated in AGRPPdk1(-/-) neurons compared to control neurons. However, ghrelin-induced [Ca(2+)](i) changes and leptin inhibition were restored in Delta256Foxo1(AGRP)Pdk1(-/-) mice. These results suggested that PDK1 and Foxo1 signaling pathways play important roles in the control of energy homeostasis through AGRP-independent mechanisms. |
