Cited by 228Sleep and Wakefulness ResearchAdipose Tissue and MetabolismRegulation of Appetite and Obesity

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An Orexinergic Projection from Perifornical Hypothalamus to Raphe Pallidus Increases Rat Brown Adipose Tissue Thermogenesis

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Tupone, Domenico, Madden, Christopher J., Cano, Georgina, Morrison, Shaun F.·2011·The Journal of Neuroscience

DOI 10.1523/jneurosci.3909-11.2011PMC PMC3224674

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Abstract

Orexin (hypocretin) neurons, located exclusively in the PeF-LH, which includes the perifornical area (PeF), the lateral hypothalamus (LH), and lateral portions of the medial hypothalamus, have widespread projections and influence many physiological functions, including the autonomic regulation of body temperature and energy metabolism. Narcolepsy is characterized by the loss of orexin neurons and by disrupted sleep, but also by dysregulation of body temperature and by a strong tendency for obesity. Heat production (thermogenesis) in brown adipose tissue (BAT) contributes to the maintenance of body temperature and, through energy consumption, to body weight regulation. We identified a neural substrate for the influence of orexin neurons on BAT thermogenesis in rat. Nanoinjection of orexin-A (12 pmol) into the rostral raphe pallidus (rRPa), the site of BAT sympathetic premotor neurons, produced large, sustained increases in BAT sympathetic outflow and in BAT thermogenesis. Activation of neurons in the PeF-LH also enhanced BAT thermogenesis over a long time course. Combining viral retrograde tracing from BAT, or cholera toxin subunit b tracing from rRPa, with orexin immunohistochemistry revealed synaptic connections to BAT from orexin neurons in PeF-LH and from rRPa neurons with closely apposed, varicose orexin fibers, as well as a direct, orexinergic projection from PeF-LH to rRPa. These results indicate a potent modulation of BAT thermogenesis by orexin released from the terminals of orexin neurons in PeF-LH directly into the rRPa and provide a potential mechanism contributing to the disrupted regulation of body temperature and energy metabolism in the absence of orexin.

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Authors: Tupone, D., Madden, C. J., Cano, G., & Morrison, S. F.
Affiliations: Oregon Health & Science University (US)
University of Pittsburgh (US)
Corresponding author: Tupone, Domenico
ORCID: Tupone, Domenico
Madden, Christopher J.
Morrison, Shaun F.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2011-11-02
Volume: 31
Issue: 44
Pages: 15944-15955
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.3909-11.2011
PMC: PMC3224674
OpenAlex: W2154434397
Cited by: 228
References: 92
Citations by year: 2026: 2 · 2025: 6 · 2024: 7 · 2023: 7 · 2022: 7 · 2021: 19 · 2020: 15 · 2019: 19 · 2018: 24 · 2017: 14 · 2016: 17 · 2015: 18 · 2014: 26 · 2013: 26 · 2012: 20
FWCI: 11.84
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 182 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
Funders: National Science Foundation (0918867)
American Heart Association
National Institutes of Health (P40OD010996)
National Institute of Diabetes and Digestive and Kidney Diseases (R56DK082558, DK-082558)
National Institute of Neurological Disorders and Stroke (NS040987, R01NS040987)
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords: orexin, perifornical hypothalamus, lateral hypothalamus, raphe pallidus, brown adipose tissue, thermogenesis, sympathetic outflow, thermoregulation, energy metabolism, narcolepsy, obesity, synaptic connectivity
MeSH terms: Orexins, Animals, Benzoxazoles, beta-Galactosidase, Body Temperature, Adipose Tissue, Brown, Cholera Toxin, Dose-Response Relationship, Drug, Globus Pallidus, Hypothalamus, Male, Microinjections, Naphthyridines, Neurons, Neuropeptides, Polystyrenes, Raphe Nuclei, Urea, N-Methylaspartate, Rats, Sprague-Dawley, Rats, Wistar, Gene Transfer Techniques, Neurotransmitter Agents, Excitatory Amino Acid Agonists, Thermogenesis, Intracellular Signaling Peptides and Proteins, Rats

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An Orexinergic Projection from Perifornical Hypothalamus to Raphe Pallidus Increases Rat Brown Adipose Tissue Thermogenesis

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