The hypothalamic arcuate nucleus: A key site for mediating leptin's effects on glucose homeostasis and locomotor activity

Roberto Coppari, Masumi Ichinose, Charlotte E. Lee, Abigail E. Pullen, Christopher D. Kenny, Robert A. McGovern, Vinsee Tang, Shun M. Liu, Thomas Ludwig, Streamson C. Chua, Bradford B. Lowell, Joel K. Elmquist

Research output: Contribution to journalArticle

332 Scopus citations

Abstract

Leptin is required for normal energy and glucose homeostasis. The hypothalamic arcuate nucleus (ARH) has been proposed as an important site of leptin action. To assess the physiological significance of leptin signaling in the ARH, we used mice homozygous for a FLPe-reactivatable, leptin receptor null allele (Leprneo/neo mice). Similar to Leprdb/db mice, these mice are obese, hyperglycemic, hyperinsulinemic, infertile, and hypoactive. To selectively restore leptin signaling in the ARH, we generated an adeno-associated virus expressing FLPe-recombinase, which was delivered unilaterally into the hypothalamus using stereotaxic injections. We found that unilateral restoration of leptin signaling in the ARH of Leprneo/neo mice leads to a modest decrease in body weight and food intake. In contrast, unilateral reactivation markedly improved hyperinsulinemia and normalized blood glucose levels and locomotor activity. These data demonstrate that leptin signaling in the ARH is sufficient for mediating leptin's effects on glucose homeostasis and locomotor activity.

Original languageEnglish (US)
Pages (from-to)63-72
Number of pages10
JournalCell metabolism
Volume1
Issue number1
DOIs
StatePublished - Jan 1 2005
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Coppari, R., Ichinose, M., Lee, C. E., Pullen, A. E., Kenny, C. D., McGovern, R. A., Tang, V., Liu, S. M., Ludwig, T., Chua, S. C., Lowell, B. B., & Elmquist, J. K. (2005). The hypothalamic arcuate nucleus: A key site for mediating leptin's effects on glucose homeostasis and locomotor activity. Cell metabolism, 1(1), 63-72. https://doi.org/10.1016/j.cmet.2004.12.004