Appropriate inhibition of orexigenic hypothalamic arcuate nucleus neurons independently of leptin receptor/STAT3 signaling
| Autor: | Rebecca L. Leshan, Joel K. Elmquist, Justin C. Jones, Sarah H. Bates, Erin E Jobst, Maria Bjornholm, Eneida C. Villanueva, Michael A. Cowley, Heike Münzberg, Martin G. Myers, Mark W. Sleeman |
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| Rok vydání: | 2007 |
| Předmět: |
STAT3 Transcription Factor
medicine.medical_specialty Action Potentials Receptors Cell Surface c-Fos Mice Proopiomelanocortin Internal medicine Orexigenic medicine Premovement neuronal activity Animals STAT3 Mice Knockout Neurons Orexins Leptin receptor biology General Neuroscience Leptin digestive oral and skin physiology Neuropeptides Arcuate Nucleus of Hypothalamus Intracellular Signaling Peptides and Proteins Neural Inhibition Articles Endocrinology nervous system Hypothalamus biology.protein Receptors Leptin hormones hormone substitutes and hormone antagonists medicine.drug Signal Transduction |
| Zdroj: | The Journal of neuroscience : the official journal of the Society for Neuroscience. 27(1) |
| ISSN: | 1529-2401 |
| Popis: | Leptin directly suppresses the activity of orexigenic neurons in the hypothalamic arcuate nucleus (ARC). We examined c-Fos-like immunoreactivity (CFLIR) as a marker of ARC neuronal activity indb/dbmice devoid of the signaling form of the leptin receptor (LRb) ands/smice that express LRbS1138[which is defective for STAT3 (signal transducer and activator of transcription) signaling]. Bothdb/dbands/sanimals are hyperphagic and obese. This analysis revealed that CFLIR in agouti related peptide-expressing orexigenic ARC neurons is basally elevated indb/dbbut nots/smice. Consistent with these observations, electrophysiologic evaluation of a small number of neurons ins/sanimals suggested that leptin appropriately suppresses the frequency of IPSCs on ARC proopiomelanocortin (POMC) neurons that are mediated by the release of GABA from orexigenic ARC neurons. CFLIR in POMC neurons ofs/smice was also increased compared withdb/dbanimals. Thus, these data suggest that, although LRb→STAT3 signaling is crucial for the regulation of feeding, it is not required for the acute or chronic regulation of orexigenic ARC neurons, and the activation of STAT3-mediated transcription by leptin is not required for the appropriate development of leptin responsiveness in these neurons. |
| Databáze: | OpenAIRE |
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