title: Promotion of Wakefulness and Energy Expenditure by Orexin-A in the Ventrolateral Preoptic Area.
abstract: OBJECTIVE
  The ventrolateral preoptic area (VLPO) and the orexin/hypocretin neuronal system are key regulators of sleep onset, transitions between vigilance states, and energy homeostasis. Reciprocal projections exist between the VLPO and orexin/hypocretin neurons. Although the importance of the VLPO to sleep regulation is clear, it is unknown whether VLPO neurons are involved in energy balance. The purpose of these studies was to determine if the VLPO is a site of action for orexin-A, and which orexin receptor subtype(s) would mediate these effects of orexin-A. We hypothesized that orexin-A in the VLPO modulates behaviors (sleep and wakefulness, feeding, spontaneous physical activity [SPA]) to increase energy expenditure.
  
  
  METHODS
  Sleep, wakefulness, SPA, feeding, and energy expenditure were determined after orexin-A microinjection in the VLPO of male Sprague-Dawley rats with unilateral cannulae targeting the VLPO. We also tested whether pretreatment with a dual orexin receptor antagonist (DORA, TCS-1102) or an OX2R antagonist (JNJ-10397049) blocked the effects of orexin-A on the sleep/wake cycle or SPA, respectively.
  
  
  RESULTS
  Orexin-A injected into the VLPO significantly increased wakefulness, SPA, and energy expenditure (SPA-induced and total) and reduced NREM sleep and REM sleep with no effect on food intake. Pretreatment with DORA blocked the increase in wakefulness and the reduction in NREM sleep elicited by orexin-A, and the OX2R antagonist reduced SPA stimulated by orexin-A.
  
  
  CONCLUSIONS
  These data show the ventrolateral preoptic area is a site of action for orexin-A, which may promote negative energy balance by modulating sleep/wakefulness and stimulating spontaneous physical activity and energy expenditure.
authors.affiliation: Minneapolis VA Health Care System, Minneapolis, MN.
authors.forename: Vijayakumar
authors.initials: V
authors.lastname: Mavanji
authors.affiliation: Center for Integrative Medicine and Innovative Science, Universidad Andres Bello, Santiago, Chile.|Escuela de Nutricion, Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.
authors.forename: Claudio E
authors.initials: CE
authors.lastname: Perez-Leighton
authors.affiliation: Minneapolis VA Health Care System, Minneapolis, MN.|Geriatric Research Education and Clinical Center, Minneapolis, MN.|Minnesota Obesity Center, University of Minnesota, Saint Paul, MN.|Department of Food Science and Nutrition, University of Minnesota, Saint Paul, MN.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Kotz
authors.affiliation: Minneapolis VA Health Care System, Minneapolis, MN.|Minnesota Obesity Center, University of Minnesota, Saint Paul, MN.|Department of Medicine, University of Minnesota, Saint Paul, MN.|Department of Food Science and Nutrition, University of Minnesota, Saint Paul, MN.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Billington
authors.affiliation: Arizona Respiratory Center University of Arizona, Tucson, AZ.|Department of Medicine University of Arizona, Tucson, AZ.
authors.forename: Sairam
authors.initials: S
authors.lastname: Parthasarathy
authors.affiliation: Arizona Respiratory Center University of Arizona, Tucson, AZ.|Department of Medicine University of Arizona, Tucson, AZ.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Sinton
authors.affiliation: Department of Nutritional Sciences, University of Arizona, Tucson, AZ.|Minneapolis VA Health Care System, Minneapolis, MN.|Minnesota Obesity Center, University of Minnesota, Saint Paul, MN.|Department of Food Science and Nutrition, University of Minnesota, Saint Paul, MN.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Teske
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects / Q000502:physiology; D004146:Dioxanes / Q000494:pharmacology; D004435:Eating / Q000187:drug effects / Q000502:physiology; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D000068796:Orexin Receptor Antagonists / Q000494:pharmacology; D064446:Orexin Receptors / Q000378:metabolism; D000068797:Orexins / Q000378:metabolism*; D010671:Phenylurea Compounds / Q000494:pharmacology; D011301:Preoptic Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D012892:Sleep Deprivation / Q000503:physiopathology; D013997:Time Factors; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*
chemical_list: D004146:Dioxanes; C524573:JNJ 10397049; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D000068797:Orexins; D010671:Phenylurea Compounds
keywords: arousal; brain; obesity; sleep
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