| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
1University of Washington and Harborview Medical Center, Seattle, Washington; 2Pennington Biomedical Research Center, Baton Rouge, Louisiana; and 3Vanderbilt University, Nashville, Tennessee
Submitted 2 March 2005 ; accepted in final form 22 July 2005
Phosphatidylinositol 3-OH-kinase (PI3K) and STAT3 are signal transduction molecules activated by leptin in brain areas controlling food intake. To investigate their role in leptin-mediated inhibition of hypothalamic neuropeptide Y (Npy) and agouti-related peptide (Agrp) gene expression, male Sprague-Dawley rats (n = 5/group) were either fed ad libitum or subjected to a 52-h fast. At 12-h intervals, the PI3K inhibitor LY-294002 (LY, 1 nmol) or vehicle was injected intracerebroventricularly (ICV) as a pretreatment, followed 1 h later by leptin (3 µg icv) or vehicle. Fasting increased hypothalamic Npy and Agrp mRNA levels (P < 0.05), and ICV leptin administration prevented this increase. As predicted, LY pretreatment blocked this inhibitory effect of leptin, such that Npy and Agrp levels in LY-leptin-treated animals were similar to fasted controls. By comparison, leptin-mediated activation of hypothalamic STAT3 signaling, as measured by induction of both phospho-STAT3 immunohistochemistry and suppressor of cytokine signaling-3 (Socs3) mRNA, was not significantly attenuated by ICV LY pretreatment. Because NPY/AgRP neurons project to the hypothalamic paraventricular nucleus (PVN), we next investigated whether leptin activation of PVN neurons is similarly PI3K dependent. Compared with vehicle, leptin increased the number of c-Fos positive cells within the parvocellular PVN (P = 0.001), and LY pretreatment attenuated this effect by 35% (P = 0.043). We conclude that leptin requires intact PI3K signaling both to inhibit hypothalamic Npy and Agrp gene expression and activate neurons within the PVN. In addition, these data suggest that leptin activation of STAT3 is insufficient to inhibit expression of Npy or Agrp in the absence of PI3K signaling.
suppressor of cytokine signaling-3; signal transducer and activator of transcription 3
This article has been cited by other articles:
|
|
 |
|
  H. Zheng and H.-R. Berthoud Neural Systems Controlling the Drive to Eat: Mind Versus Metabolism Physiology, April 1, 2008; 23(2): 75 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Shimizu, K. Inoue, and M. Mori The leptin-dependent and -independent melanocortin signaling system: regulation of feeding and energy expenditure J. Endocrinol., April 1, 2007; 193(1): 1 - 9. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Kraemer and V. D. Castracane Exercise and Humoral Mediators of Peripheral Energy Balance: Ghrelin and Adiponectin Experimental Biology and Medicine, February 1, 2007; 232(2): 184 - 194. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Akhter, B. W. Johnson, C. Crane, M. Iruthayanathan, Y.-H. Zhou, A. Kudo, and G. V. Childs Anterior Pituitary Leptin Expression Changes in Different Reproductive States: In Vitro Stimulation by Gonadotropin-releasing Hormone J. Histochem. Cytochem., February 1, 2007; 55(2): 151 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-S. Hsieh, S.-F. Yang, and D.-Y. Kuo Intracerebral administration of protein kinase A or cAMP response element-binding protein antisense oligonucleotide can modulate amphetamine-mediated appetite suppression in free-moving rats Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E123 - E131. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
