Developmental changes in hypothalamic leptin receptor: relationship with the postnatal leptin surge and energy balance neuropeptides in the postnatal rat

E. C. Cottrell, R. L. Cripps, Jacqueline Duncan, Perry Barrett, Julian Mercer, Annika Herwig, S. E. Ozanne

Research output: Contribution to journalArticle

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Abstract

Cottrell EC, Cripps RL, Duncan JS, Barrett P, Mercer JG, Herwig A, Ozanne SE. Developmental changes in hypothalamic leptin receptor: relationship with the postnatal leptin surge and energy balance neuropeptides in the postnatal rat. Am J Physiol Regul Integr Comp Physiol 296: R631-R639, 2009. First published January 14, 2009; doi: 10.1152/ajpregu.90690.2008.- In the adult brain, leptin regulates energy homeostasisprimarily via hypothalamic circuitry that affects food intake and energy expenditure. Evidence from rodent models has demonstrated that during early postnatal life, leptin is relatively ineffective in modulating these pathways, despite the high circulating levels and the presence of leptin receptors within the central nervous system. Furthermore, in recent years, a neurotrophic role for leptin in the establishment of energy balance circuits has emerged. The precise way in which leptin exerts these effects, and the site of leptin action, is unclear. To provide a detailed description of the development of energy balance systems in the postnatal rat in relation to leptin concentrations during this time, endogenous leptin levels were measured, along with gene expression of leptin receptors and energy balance neuropeptides in the medial basal hypothalamus, using in situ hybridization. Expression of leptin receptors and both orexigenic and anorexigenic neuropeptides increased in the arcuate nucleus during the early postnatal period. At postnatal day 4 (P4), we detected dense leptin receptor expression in ependymal cells of the third ventricle (3V), which showed a dramatic reduction over the first postnatal weeks, coinciding with marked morphological changes in this region. An acute leptin challenge robustly induced suppressor of cytokine signaling-3 expression in the 3V of P4 but not P14 animals, revealing a clear change in the location of leptin action over this period. These findings suggest that the neurotrophic actions of leptin may involve signaling at the 3V during a restricted period of postnatal development.

Original languageEnglish
Pages (from-to)R631-R639
Number of pages9
JournalAmerican Journal of Physiology-Regulatory Integrative and Comparative Physiology
Volume296
Issue number3
DOIs
Publication statusPublished - Mar 2009

Keywords

  • neonate
  • hypothalamus
  • development
  • central-nervous-system
  • gene-expression
  • arcuate nucleus
  • messenger-RNA
  • mouse hypothalamus
  • long-form
  • settling patterns
  • Siberian hamster
  • food-intake
  • OB-RB

Cite this

Developmental changes in hypothalamic leptin receptor : relationship with the postnatal leptin surge and energy balance neuropeptides in the postnatal rat. / Cottrell, E. C.; Cripps, R. L.; Duncan, Jacqueline; Barrett, Perry; Mercer, Julian; Herwig, Annika; Ozanne, S. E.

In: American Journal of Physiology-Regulatory Integrative and Comparative Physiology, Vol. 296, No. 3, 03.2009, p. R631-R639.

Research output: Contribution to journalArticle

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