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The Action of Leptin on Appetite-Regulating Cells in the Ovine Hypothalamus: Demonstration of Direct Action in the Absence of the Arcuate Nucleus
- Source :
- Endocrinology. 151:2106-2116
- Publication Year :
- 2010
- Publisher :
- The Endocrine Society, 2010.
-
Abstract
- It is widely accepted that leptin acts on first-order neurons in the arcuate nucleus (ARC) with information then relayed to other hypothalamic centers. However, the extent to which leptin mediates its central actions solely, or even primarily, via this route is unclear. We used a model of hypothalamo-pituitary disconnection (HPD) to determine whether leptin action on appetite-regulating systems requires the ARC. This surgical preparation eliminates the ARC. We measured effects of iv leptin to activate hypothalamic neurons (Fos labeling). In ARC-intact animals, leptin increased the percentage of Fos-positive melanocortin neurons and reduced percentages of Fos-positive neuropeptide Y neurons compared with saline-treated animals. HPD itself increased Fos labeling in the lateral hypothalamic area (LHA). Leptin influenced Fos labeling in the dorsomedial nucleus (DMH), ventromedial nucleus, and paraventricular nucleus (PVN) in HPD and normal animals, with effects on particular cell types varying. In the LHA and DMH, leptin decreased orexin cell activation in HPD and ARC-intact sheep. HPD abolished leptin-induced expression of Fos in melanin-concentrating hormone cells in the LHA and in CRH cells in the PVN. In contrast, HPD accentuated activation in oxytocin neurons. Our data from sheep with lesions encompassing the ARC do not suggest a primacy of action of leptin in this nucleus. We demonstrate that first order to second order signaling may not represent the predominant means by which leptin acts in the brain to generate integrated responses. We provide evidence that leptin exerts direct action on cells of the DMH, ventromedial nucleus, and PVN.
- Subjects :
- Leptin
endocrine system
medicine.medical_specialty
Hypothalamus
Appetite
Dorsomedial Hypothalamic Nucleus
Biology
Endocrinology
Arcuate nucleus
Internal medicine
medicine
Animals
Neurons
Sheep
Neuropeptides
digestive, oral, and skin physiology
Arcuate Nucleus of Hypothalamus
Neuropeptide Y receptor
Immunohistochemistry
Orexin
medicine.anatomical_structure
nervous system
Oxytocin
Ventromedial Hypothalamic Nucleus
Hypothalamic Area, Lateral
Pituitary Gland
Injections, Intravenous
Female
Cell activation
Proto-Oncogene Proteins c-fos
Nucleus
hormones, hormone substitutes, and hormone antagonists
Paraventricular Hypothalamic Nucleus
medicine.drug
Subjects
Details
- ISSN :
- 19457170 and 00137227
- Volume :
- 151
- Database :
- OpenAIRE
- Journal :
- Endocrinology
- Accession number :
- edsair.doi.dedup.....06d8c0c9e7b853ca40503ac379708ad1
- Full Text :
- https://doi.org/10.1210/en.2009-1283