Leptin Sensitivity in the Developing Rat Hypothalamus

A. -S. Carlo, M. Pyrski, C. Loudes, A. Faivre-Baumann, J. Epelbaum, Lynda Williams, W. Meyerhof

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

In adults, the adipocyte-derived hormone, leptin, regulates food intake and body weight principally via the hypothalamic arcuate nucleus ( ARC). During early postnatal development, leptin functions to promote the outgrowth of neuronal projections from the ARC, whereas a selective insensitivity to the effects of leptin on food intake appears to exist. To investigate the mechanisms underlying the inability of leptin to regulate food intake during early development, leptin signaling was analyzed both in vitro using primary cultures of rat embryonic ARC neurones and in vivo by challenging early postnatal rats with leptin. In neuronal cultures, despite the presence of key components of the leptin signaling pathway, no detectable activation of either signal transducer and activator of transcription 3 or the MAPK pathways by leptin was detected. However, leptin down-regulated mRNA levels of proopiomelanocortin and neuropeptide Y and decreased somatostatin secretion. Leptin challenge in vivo at postnatal d ( P) 7, P14, P21, and P28 revealed that, in contrast to adult and P28 rats, mRNA levels of neuropeptide Y, proopiomelanocortin, agouti-related peptide and cocaine- and amphetamine-regulated transcript were largely unaffected at P7, P14, and P21. Furthermore, leptin stimulation increased the suppressor of cytokine signaling-3mRNA levels at P14, P21, and P28 in several hypothalamic nuclei but not at P7, indicating that selective leptin insensitivity in the hypothalamus is coupled to developmental shifts in leptin receptor signaling. Thus, the present study defines the onset of leptin sensitivity in the regulation of energy homeostasis in the developing hypothalamus.

Original languageEnglish
Pages (from-to)6073-6082
Number of pages10
JournalEndocrinology
Volume148
Issue number12
Early online date13 Sep 2007
DOIs
Publication statusPublished - 1 Dec 2007

Keywords

  • proopiomelanocortin messenger-RNA
  • body-weight regulation
  • central-nervous-system
  • neuropeptide-Y NPY
  • arcuate nucleus
  • gene-expression
  • energy-balance
  • OB/OB mice
  • long-form
  • signal transducer

Cite this

Carlo, A. -S., Pyrski, M., Loudes, C., Faivre-Baumann, A., Epelbaum, J., Williams, L., & Meyerhof, W. (2007). Leptin Sensitivity in the Developing Rat Hypothalamus. Endocrinology, 148(12), 6073-6082. https://doi.org/10.1210/en.2007-0822

Leptin Sensitivity in the Developing Rat Hypothalamus. / Carlo, A. -S.; Pyrski, M.; Loudes, C.; Faivre-Baumann, A.; Epelbaum, J.; Williams, Lynda; Meyerhof, W.

In: Endocrinology, Vol. 148, No. 12, 01.12.2007, p. 6073-6082.

Research output: Contribution to journalArticle

Carlo, A-S, Pyrski, M, Loudes, C, Faivre-Baumann, A, Epelbaum, J, Williams, L & Meyerhof, W 2007, 'Leptin Sensitivity in the Developing Rat Hypothalamus', Endocrinology, vol. 148, no. 12, pp. 6073-6082. https://doi.org/10.1210/en.2007-0822
Carlo A-S, Pyrski M, Loudes C, Faivre-Baumann A, Epelbaum J, Williams L et al. Leptin Sensitivity in the Developing Rat Hypothalamus. Endocrinology. 2007 Dec 1;148(12):6073-6082. https://doi.org/10.1210/en.2007-0822
Carlo, A. -S. ; Pyrski, M. ; Loudes, C. ; Faivre-Baumann, A. ; Epelbaum, J. ; Williams, Lynda ; Meyerhof, W. / Leptin Sensitivity in the Developing Rat Hypothalamus. In: Endocrinology. 2007 ; Vol. 148, No. 12. pp. 6073-6082.
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