The anorexigenic cytokine ciliary neurotrophic factor stimulates POMC gene expression via receptors localized in the nucleus of arcuate neurons

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 correl...

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Published inAmerican journal of physiology: endocrinology and metabolism Vol. 302; no. 4; pp. E458 - E467
Main Authors Couvreur, Odile, Aubourg, Alain, Crépin, Delphine, Degrouard, Jéril, Gertler, Arieh, Taouis, Mohammed, Vacher, Claire-Marie
Format Journal Article
LanguageEnglish
Published United States American Physiological Society 15.02.2012
Subjects
Animals
Arcuate Nucleus of Hypothalamus - metabolism
Cell Nucleus - metabolism
Ciliary Neurotrophic Factor - metabolism
Ciliary Neurotrophic Factor Receptor alpha Subunit - genetics
Ciliary Neurotrophic Factor Receptor alpha Subunit - metabolism
Cytokines
Gene Expression
Gene Expression Regulation
Homeostasis
Life Sciences
Male
Neurons
Neurons and Cognition
Phosphorylation
Pro-Opiomelanocortin - genetics
Rats
Rats, Wistar
Rodents
Signal Transduction - physiology
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Summary: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.
ISSN:0193-1849
1522-1555
DOI:10.1152/ajpendo.00388.2011