The anorexigenic cytokine Ciliary Neurotrophic Factor (CNTF) stimulates POMC gene expression via receptors localized in the nucleus of arcuate neurons
| Autor: | Alain Aubourg, Claire-Marie Vacher, Jéril Degrouard, Delphine Crépin, Arieh Gertler, Odile Couvreur, Mohammed Taouis |
|---|---|
| Přispěvatelé: | Centre de Neurosciences Paris-Sud (CNPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Développement et évolution (DE), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Food Science, and Nutrition, Faculty of Agricultural, Food and Environmental Quality Sciences |
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Pomc gene
Male medicine.medical_specialty Pro-Opiomelanocortin Physiology Endocrinology Diabetes and Metabolism medicine.medical_treatment media_common.quotation_subject Gene Expression Ciliary neurotrophic factor Energy homeostasis 03 medical and health sciences 0302 clinical medicine Physiology (medical) Internal medicine medicine Animals Ciliary Neurotrophic Factor Phosphorylation Rats Wistar Receptor 030304 developmental biology media_common Cell Nucleus 0303 health sciences biology Arcuate Nucleus of Hypothalamus Appetite Rats Cytokine Endocrinology medicine.anatomical_structure Gene Expression Regulation biology.protein [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] Signal transduction Nucleus 030217 neurology & neurosurgery Ciliary Neurotrophic Factor Receptor alpha Subunit Signal Transduction |
| Zdroj: | AJP-Endocrinology and Metabolism AJP-Endocrinology and Metabolism, American Physiological Society, 2012, 302 (4), pp.E458-67. ⟨10.1152/ajpendo.00388.2011⟩ |
| ISSN: | 0193-1849 1522-1555 |
| Popis: | International audience; Ciliary neurotrophic factor (CNTF) is a neural cytokine that reduces appetite and body weight when administrated to rodents or humans. We have demonstrated recently that the level of CNTF in the arcuate nucleus (ARC), a key hypothalamic region involved in food intake regulation, is positively correlated with protection against diet-induced obesity. However, the comprehension of the physiological significance of neural CNTF action was still incomplete because CNTF lacks a signal peptide and thus may not be secreted by the classical exocytosis pathways. Knowing that CNTF distribution shares similarities with that of its receptor subunits in the rat ARC, we hypothesized that CNTF could exert a direct intracrine effect in ARC cells. Here, we demonstrate that CNTF, together with its receptor subunits, translocates to the cell nucleus of anorexigenic POMC neurons in the rat ARC. Furthermore, the stimulation of hypothalamic nuclear fractions with CNTF induces the phosphorylation of several signaling proteins, including Akt, as well as the transcription of the POMC gene. These data strongly suggest that intracellular CNTF may directly modulate POMC gene expression via the activation of receptors localized in the cell nucleus, providing a novel plausible mechanism of CNTF action in regulating energy homeostasis. |
| Databáze: | OpenAIRE |
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