Gp130 Signaling in Proopiomelanocortin Neurons Mediates the Acute Anorectic Response to Centrally Applied Ciliary Neurotrophic Factor

Ciliary neurotrophic factor (CNTF) exerts anorectic effects by overcoming leptin resistance via activation of hypothalamic neurons. However, the exact site of CNTF action in the hypothalamus has not yet been identified. Using Cre-loxP-mediated recombination in vivo, we have selectively ablated the c...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-07, Vol.103 (28), p.10707-10712
Main Authors: Janoschek, Ruth, Plum, Leona, Koch, Linda, Münzberg, Heike, Diano, Sabrina, Shanabrough, Marya, Müller, Werner, Horvath, Tamas L., Brüning, Jens C.
Format: Article
Language:English
Subjects:
Acute Disease
Animals
Anorexia
Anorexia - genetics
Anorexia - metabolism
Antibodies
Appetite depressants
Biological Sciences
Body weight
Ciliary Neurotrophic Factor - administration & dosage
Ciliary Neurotrophic Factor - physiology
Cytokine Receptor gp130 - genetics
Cytokine Receptor gp130 - physiology
Female
Food intake
Homeostasis
Hypothalamus
Injections, Intraventricular
Male
Metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Mutant Strains
Neurons
Neurons - physiology
Obesity
Pro-Opiomelanocortin - biosynthesis
Pro-Opiomelanocortin - physiology
Rats
Receptors
Rodents
Signal Transduction - genetics
Signal Transduction - physiology
Signaling
Studies
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Summary:Ciliary neurotrophic factor (CNTF) exerts anorectic effects by overcoming leptin resistance via activation of hypothalamic neurons. However, the exact site of CNTF action in the hypothalamus has not yet been identified. Using Cre-loxP-mediated recombination in vivo, we have selectively ablated the common cytokine signaling chain gp130, which is required for functional CNTF signaling, in proopiomelanocortin (POMC)-expressing neurons. POMC-specific gp130 knockout mice exhibit unaltered numbers of POMC cells and normal energy homeostasis under standard and high fat diet. Endotoxin (LPS) and stress-induced anorexia and adrenocorticotropin regulation were unaffected in these animals. Strikingly, the anorectic effect of centrally administered CNTF was abolished in POMC-specific gp130 knockout mice. Correspondingly, in these animals, CNTF failed to activate STAT3 phosphorylation in POMC neurons and to induce c-Fos expression in the paraventricular nucleus. These data reveal POMC neurons as a critical site of CNTF action in mediating its anorectic effect.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0600425103