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

Authors
  • Coppari, Roberto
  • Ichinose, Masumi
  • Lee, Charlotte E
  • Pullen, Abigail E
  • Kenny, Christopher D
  • McGovern, Robert A
  • Tang, Vinsee
  • Liu, Shun M
  • Ludwig, Thomas
  • Chua, Streamson C Jr
  • Lowell, Bradford B
  • Elmquist, Joel K
Type
Published Article
Journal
Cell Metabolism
Publisher
Elsevier
Publication Date
Jan 01, 2005
Volume
1
Issue
1
Pages
63–72
Identifiers
PMID: 16054045
Source
Medline
License
Unknown

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 (Lepr(neo/neo) mice). Similar to Lepr(db/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 Lepr(neo/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.

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