Ciliary Neurotrophic Factor and Leptin Induce Distinct Patterns of Immediate Early Gene Expression in the Brain

Joseph F. Kelly, Carol F. Elias, Charlotte E. Lee, Rexford S. Ahima, Randy J. Seeley, Christian Bjørbæk, Takakazu Oka, Clifford B. Saper, Jeffrey S. Flier, Joel K. Elmquist

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Ciliary neurotrophic factor (CNTF) and leptin decrease food intake and body weight. Lipopolysaccharide (LPS) is a potent exogenous pyrogen and produces anorexia via cytokine production. CNTF-, leptin-, and LPS-induced cytokines all act on type I cytokine receptors. However, it is not known if these cytokines engage similar central nervous system (CNS) pathways to exert their effects. To assess mechanisms by which these cytokines act, we examined the patterns of immediate early gene expression (SOCS-3, c-fos, and tis-11) in the brain following intravenous administration. CNTF and LPS induced gene expression in circumventricular organs; ependymal cells of the ventricles, meninges, and choroid plexus; and the arcuate nucleus of the hypothalamus. CNTF administration also induced fever and cyclooxygenase-2 mRNA expression. In contrast, we found no evidence of leptin-induced inflammation. CNTF and leptin are being assessed as potential therapeutic anti-obesity agents, and both potently reduce food intake. Our findings support the hypothesis that CNTF and leptin engage distinct CNS sites and CNTF possesses inflammatory properties distinct from leptin.

Original languageEnglish (US)
Pages (from-to)911-920
Number of pages10
JournalDiabetes
Volume53
Issue number4
DOIs
StatePublished - Apr 2004

Fingerprint

Ciliary Neurotrophic Factor
Immediate-Early Genes
Leptin
Gene Expression
Brain
Cytokines
Lipopolysaccharides
Central Nervous System
Eating
Anti-Obesity Agents
Pyrogens
Meninges
Arcuate Nucleus of Hypothalamus
Cytokine Receptors
Choroid Plexus
Anorexia
Cyclooxygenase 2
Intravenous Administration
Fever
Body Weight

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Ciliary Neurotrophic Factor and Leptin Induce Distinct Patterns of Immediate Early Gene Expression in the Brain. / Kelly, Joseph F.; Elias, Carol F.; Lee, Charlotte E.; Ahima, Rexford S.; Seeley, Randy J.; Bjørbæk, Christian; Oka, Takakazu; Saper, Clifford B.; Flier, Jeffrey S.; Elmquist, Joel K.

In: Diabetes, Vol. 53, No. 4, 04.2004, p. 911-920.

Research output: Contribution to journalArticle

Kelly, JF, Elias, CF, Lee, CE, Ahima, RS, Seeley, RJ, Bjørbæk, C, Oka, T, Saper, CB, Flier, JS & Elmquist, JK 2004, 'Ciliary Neurotrophic Factor and Leptin Induce Distinct Patterns of Immediate Early Gene Expression in the Brain', Diabetes, vol. 53, no. 4, pp. 911-920. https://doi.org/10.2337/diabetes.53.4.911
Kelly, Joseph F. ; Elias, Carol F. ; Lee, Charlotte E. ; Ahima, Rexford S. ; Seeley, Randy J. ; Bjørbæk, Christian ; Oka, Takakazu ; Saper, Clifford B. ; Flier, Jeffrey S. ; Elmquist, Joel K. / Ciliary Neurotrophic Factor and Leptin Induce Distinct Patterns of Immediate Early Gene Expression in the Brain. In: Diabetes. 2004 ; Vol. 53, No. 4. pp. 911-920.
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