Ciliary neurotrophic factor corrects obesity and diabetes associated with leptin deficiency and resistance

Isabelle Gloaguen, Patrizia Costa, Anna Demartis, Domenico Lazzaro, Annalise Di Marco, Rita Graziani, Giacomo Paonessa, Fang Chen, Charles I. Rosenblum, Lex H T Van Der Ploeg, Riccardo Cortese, Gennaro Ciliberto, Ralph Laufer

Research output: Contribution to journalArticlepeer-review

Abstract

Receptor subunits for the neurocytokine ciliary neurotrophic factor (CNTF) share sequence similarity with the receptor for leptin, an adipocyte- derived cytokine involved in body weight homeostasis. We report here that CNTF and leptin activate a similar pattern of STAT factors in neuronal cells, and that mRNAs for CNTF receptor subunits, similarly to the mRNA of leptin receptor, are localized in mouse hypothalamic nuclei involved in the regulation of energy balance. Systemic administration of CNTF or leptin led to rapid induction of the tis-11 primary response gene in the arcuate nucleus, suggesting that both cytokines can signal to hypothalamic satiety centers. Consistent with this idea, CNTF treatment of ob/ob mice, which lack functional leptin, was found to reduce the adiposity, hyperphagia, and hyperinsulinemia associated with leptin deficiency. Unlike leptin, CNTF also reduced obesity-related phenotypes in db/db mice, which lack functional leptin receptor, and in mice with diet-induced obesity, which are partially resistant to the actions of leptin. The identification of a cytokine-mediated anti-obesity mechanism that acts independently of the leptin system may help to develop strategies for the treatment of obesity associated with leptin resistance.

Original languageEnglish
Pages (from-to)6456-6461
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number12
DOIs
Publication statusPublished - Jun 10 1997

ASJC Scopus subject areas

  • Genetics
  • General

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