The hypothalamic arcuate nucleus: A key site for mediating leptin’s effects on glucose homeostasis and locomotor activity
Autor: | Joel K. Elmquist, Robert A. McGovern, Shun M. Liu, Roberto Coppari, Abigail E. Pullen, Streamson C. Chua, Charlotte E. Lee, Bradford B. Lowell, Thomas Ludwig, Masumi Ichinose, Christopher D. Kenny, Vinsee Tang |
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Rok vydání: | 2005 |
Předmět: |
Leptin
Male medicine.medical_specialty Time Factors Physiology Green Fluorescent Proteins Hypothalamus Mice Transgenic Receptors Cell Surface Motor Activity Biology Carbohydrate metabolism Mice Oxygen Consumption Internal medicine medicine Hyperinsulinemia Animals Homeostasis Glucose homeostasis Receptor Molecular Biology Alleles Cell Nucleus Neurons Leptin receptor Models Genetic Body Weight Homozygote digestive oral and skin physiology Arcuate Nucleus of Hypothalamus Cell Biology medicine.disease Immunohistochemistry Mice Inbred C57BL Fertility Glucose Endocrinology DNA Nucleotidyltransferases Body Composition Receptors Leptin hormones hormone substitutes and hormone antagonists Signal Transduction |
Zdroj: | Cell Metabolism. 1:63-72 |
ISSN: | 1550-4131 |
Popis: | SummaryLeptin 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. |
Databáze: | OpenAIRE |
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