An Orexinergic Projection from Perifornical Hypothalamus to Raphe Pallidus Increases Rat Brown Adipose Tissue Thermogenesis
Open Access
- 2 November 2011
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 31 (44), 15944-15955
- https://doi.org/10.1523/jneurosci.3909-11.2011
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.Keywords
This publication has 56 references indexed in Scilit:
- Central efferent pathways for cold‐defensive and febrile shiveringThe Journal of Physiology, 2011
- 2010 Carl Ludwig Distinguished Lectureship of the APS Neural Control and Autonomic Regulation Section: Central neural pathways for thermoregulatory cold defenseJournal of Applied Physiology, 2011
- Brown Adipose Tissue in Morbidly Obese SubjectsPLOS ONE, 2011
- The neuroendocrine basis of lactation-induced suppression of GnRH: Role of kisspeptin and leptinBrain Research, 2010
- Brown Fat and the Myth of Diet-Induced ThermogenesisCell Metabolism, 2010
- Parallel Preoptic Pathways for ThermoregulationJournal of Neuroscience, 2009
- The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissueThe FASEB Journal, 2009
- Enhanced Orexin Receptor-2 Signaling Prevents Diet-Induced Obesity and Improves Leptin SensitivityCell Metabolism, 2009
- A thermosensory pathway that controls body temperatureNature Neuroscience, 2007
- Central efferent pathways mediating skin cooling-evoked sympathetic thermogenesis in brown adipose tissueAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2007