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Evidence That the Caudal Brainstem Is a Target for the Inhibitory Effect of Leptin on Food Intake
Abstract
Three experiments were performed to investigate the hypothesis that leptin action within the caudal brain stem (CBS) contributes to its intake inhibitory effects. The first experiment evaluated the anatomical distribution of leptin receptor mRNA in rat CBS using a sensitive fluorescence in situ hybridization method with a riboprobe specific for the long form of the leptin receptor (Ob-Rb). An Ob-Rb mRNA hybridization signal was detected in neurons of several CBS nuclei involved in the control of food intake, including the dorsal vagal complex and parabrachial nucleus. A strong hybridization signal was also obtained from neuronal cell bodies of a number of other structures including the hypoglossal, trigeminal, lateral reticular, and cochlear nuclei; locus ceruleus; and inferior olive. The anatomical profile revealed by fluorescence in situ hybridization was in good agreement with immunocytochemical analysis with an antibody specific to Ob-Rb. In a second experiment, exploring the relevance of CBS Ob-Rb to feeding behavior, rats were given a fourth intracerebroventricular (i.c.v.) injection of leptin (0.1, 0.83, or 5.0μ g; n = 9–11/group) or vehicle 30 min before lights-out on three consecutive days The two higher doses reduced food intake significantly at 2, 4, and 24 h after injection and caused significant reductions of body weight. The dose-response profiles for fourth i.c.v. administration were indistinguishable from those obtained from separate groups of rats that received leptin via a lateral i.c.v. cannula. In the last experiment, a ventricle-subthreshold dose of leptin (0.1 μg) microinjected unilaterally into the dorsal vagal complex suppressed food intake at 2, 4, and 24 h. The results indicate that the CBS contains neurons that are potentially direct targets for the action of leptin in the control of energy homeostasis.
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“functional leptin receptors are expressed in the hippocampus, hindbrain (including the nucleus of the solitary tract (NTS)), pyriform cortex and other olfactory processing areas, and in mesolimbic areas involved in reward including the ventral tegmental area (VTA) and substantia nigra (SN) (61, 72).”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [72]
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“There is evidence of leptin receptor (ObRb) mRNA in neuronal cell bodies of trigeminal motor nuclei as well as the LC, dorsal vagal complex, and parabrachial nucleus (363).”
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Metadata
- Authors
- Grill, H. J., Schwartz, M. W., Kaplan, J. M., Foxhall, J. S., Breininger, J., & Baskin, D. G.
- Affiliations
- University of Pennsylvania (US)
- University of Washington (US)
- Corresponding author
- Grill, Harvey J.
- Venue
- Endocrinology
- Publisher
- The Endocrine Society
- Published
- 2002-01-01
- Volume
- 143
- Issue
- 1
- Pages
- 239-246
- ISSN
- 0013-7227 (ISSN-L)
- 1945-7170
- OpenAlex
- W1976978438
- Cited by
- 395
- References
- 51
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 8 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 12 · 2019: 8 · 2018: 14 · 2017: 8 · 2016: 11 · 2015: 11 · 2014: 20 · 2013: 22 · 2012: 28
- FWCI
- 7.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- University of Pennsylvania
- University of Washington (DK17047)
- National Institutes of Health (2r01dk012829-36, DK21397)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 12829, R01DK042284, R01DK052989, DK-42284, DK-52989, DK-17047, DK 21397, P30DK017047)
- National Institute of Neurological Disorders and Stroke (NS-32272)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- leptin, caudal brainstem, food intake regulation, dorsal vagal complex, parabrachial nucleus, energy homeostasis, weight loss, hypothalamic-pituitary-thyroid axis
- MeSH terms
- Animals, Brain Stem, Carrier Proteins, Eating, Injections, Intraventricular, Male, Receptors, Cell Surface, Tissue Distribution, Vagus Nerve, Rats, Wistar, Protein Isoforms, Fourth Ventricle, Lateral Ventricles, Leptin, Rats, Receptors, Leptin
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