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

  1. Joseph F. Kelly12,
  2. Carol F. Elias3,
  3. Charlotte E. Lee12,
  4. Rexford S. Ahima4,
  5. Randy J. Seeley5,
  6. Christian Bjørbæk1,
  7. Takakazu Oka2,
  8. Clifford B. Saper2,
  9. Jeffrey S. Flier1 and
  10. Joel K. Elmquist12
  1. 1Department of Medicine and Division of Endocrinology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
  2. 2Department of Neurology and Program in Neuroscience, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
  3. 3Department of Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil
  4. 4Division of Endocrinology, Diabetes and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
  5. 5Department of Psychiatry, University of Cincinnati, Cincinnati, Ohio
  1. Address correspondence and reprint requests to Dr. Joel K. Elmquist, Beth Israel Deaconess Medical Center, Division of Endocrinology, 99 Brookline Ave., Boston, MA 02215. E-mail: jelmquis{at}bidmc.harvard.edu

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 antiobesity 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.

Footnotes

  • J.S.F. has received a research grant from Takeda Chemical.

    • Accepted January 20, 2004.
    • Received January 31, 2003.
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