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, Jr., Bradford B. Lowell, Joel K. Elmquist

Research output: Contribution to journalArticle

320 Citations (Scopus)

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 2005
Externally publishedYes

Fingerprint

Arcuate Nucleus of Hypothalamus
Locomotion
Leptin
Homeostasis
Glucose
Obese Mice
Leptin Receptors
Dependovirus
Recombinases
Hyperinsulinism
Hypothalamus
Blood Glucose
Eating
Alleles
Body Weight
Injections

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

Cite this

Coppari, R., Ichinose, M., Lee, C. E., Pullen, A. E., Kenny, C. D., McGovern, R. A., ... 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

The hypothalamic arcuate nucleus : A key site for mediating leptin's effects on glucose homeostasis and locomotor activity. / Coppari, Roberto; Ichinose, Masumi; Lee, Charlotte E.; Pullen, Abigail E.; Kenny, Christopher D.; McGovern, Robert A.; Tang, Vinsee; Liu, Shun M.; Ludwig, Thomas; Chua, Jr., Streamson C.; Lowell, Bradford B.; Elmquist, Joel K.

In: Cell Metabolism, Vol. 1, No. 1, 01.2005, p. 63-72.

Research output: Contribution to journalArticle

Coppari, R, Ichinose, M, Lee, CE, Pullen, AE, Kenny, CD, McGovern, RA, Tang, V, Liu, SM, Ludwig, T, Chua, Jr., SC, Lowell, BB & Elmquist, JK 2005, 'The hypothalamic arcuate nucleus: A key site for mediating leptin's effects on glucose homeostasis and locomotor activity', Cell Metabolism, vol. 1, no. 1, pp. 63-72. https://doi.org/10.1016/j.cmet.2004.12.004
Coppari, Roberto ; Ichinose, Masumi ; Lee, Charlotte E. ; Pullen, Abigail E. ; Kenny, Christopher D. ; McGovern, Robert A. ; Tang, Vinsee ; Liu, Shun M. ; Ludwig, Thomas ; Chua, Jr., Streamson C. ; Lowell, Bradford B. ; Elmquist, Joel K. / The hypothalamic arcuate nucleus : A key site for mediating leptin's effects on glucose homeostasis and locomotor activity. In: Cell Metabolism. 2005 ; Vol. 1, No. 1. pp. 63-72.
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