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An Orexinergic Projection from Perifornical Hypothalamus to Raphe Pallidus Increases Rat Brown Adipose Tissue Thermogenesis
Open accessAbstract
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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“AMP-activated protein kinase (AMPK) in the ventromedial nucleus of the hypothalamus (VMH) and orexin (OX) in the lateral hypothalamic area (LHA) modulate brown adipose tissue (BAT) thermogenesis.”
From A Functional Link between AMPK and Orexin Mediates the Effect of BMP8B on Energy Balance (2016) · cites this paper as Tupone et al., 2011
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Metadata
- 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
- 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
- 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
- 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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