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Sleep. 2015 Sep 1;38(9):1361-70. doi: 10.5665/sleep.4970.

Promotion of Wakefulness and Energy Expenditure by Orexin-A in the Ventrolateral Preoptic Area.

Author information

1
Minneapolis VA Health Care System, Minneapolis, MN.
2
Center for Integrative Medicine and Innovative Science, Universidad Andres Bello, Santiago, Chile.
3
Escuela de Nutricion, Facultad de Medicina, Universidad Andres Bello, Santiago, Chile.
4
Geriatric Research Education and Clinical Center, Minneapolis, MN.
5
Minnesota Obesity Center, University of Minnesota, Saint Paul, MN.
6
Department of Food Science and Nutrition, University of Minnesota, Saint Paul, MN.
7
Department of Medicine, University of Minnesota, Saint Paul, MN.
8
Arizona Respiratory Center University of Arizona, Tucson, AZ.
9
Department of Medicine University of Arizona, Tucson, AZ.
10
Department of Nutritional Sciences, University of Arizona, Tucson, AZ.

Abstract

STUDY OBJECTIVES:

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.

DESIGN AND MEASUREMENTS:

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.

KEYWORDS:

arousal; brain; obesity; sleep

PMID:
25845696
PMCID:
PMC4531404
DOI:
10.5665/sleep.4970
[Indexed for MEDLINE]
Free PMC Article
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