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

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.
Authors	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
Journal	Cell metabolism (Cell Metab) Vol. 1 Issue 1 Pg. 63-72 (Jan 2005) ISSN: 1550-4131 [Print] United States
PMID	16054045 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References	Leptin Receptors, Cell Surface Receptors, Leptin Green Fluorescent Proteins DNA Nucleotidyltransferases FLP recombinase Glucose
Topics	Alleles Animals Arcuate Nucleus of Hypothalamus (metabolism) Body Composition Body Weight Cell Nucleus (metabolism) DNA Nucleotidyltransferases (metabolism) Fertility Glucose (metabolism) Green Fluorescent Proteins (metabolism) Homeostasis Homozygote Hypothalamus (metabolism) Immunohistochemistry Leptin (metabolism) Male Mice Mice, Inbred C57BL Mice, Transgenic Models, Genetic Motor Activity Neurons (metabolism) Oxygen Consumption Receptors, Cell Surface (metabolism) Receptors, Leptin Signal Transduction Time Factors

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