Promotion of wakefulness and energy expenditure by orexin-a in the ventrolateral preoptic area

Vijayakumar Mavanji, Claudio E. Perez-Leighton, Catherine M. Kotz, Charles J. Billington, Sairam Parthasarathy, Christopher M. Sinton, Jennifer A. Teske

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1361-1370
Number of pages10
JournalSleep
Volume38
Issue number9
DOIs
StatePublished - Sep 1 2015

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Preoptic Area
Wakefulness
Energy Metabolism
Sleep
Orexins
Orexin Receptors
Neurons
REM Sleep
Microinjections
Sprague Dawley Rats
Homeostasis
Eating

Keywords

  • Arousal
  • Brain
  • Obesity
  • Sleep

ASJC Scopus subject areas

  • Physiology (medical)
  • Clinical Neurology

Cite this

Mavanji, V., Perez-Leighton, C. E., Kotz, C. M., Billington, C. J., Parthasarathy, S., Sinton, C. M., & Teske, J. A. (2015). Promotion of wakefulness and energy expenditure by orexin-a in the ventrolateral preoptic area. Sleep, 38(9), 1361-1370. https://doi.org/10.5665/sleep.4970

Promotion of wakefulness and energy expenditure by orexin-a in the ventrolateral preoptic area. / Mavanji, Vijayakumar; Perez-Leighton, Claudio E.; Kotz, Catherine M.; Billington, Charles J.; Parthasarathy, Sairam; Sinton, Christopher M.; Teske, Jennifer A.

In: Sleep, Vol. 38, No. 9, 01.09.2015, p. 1361-1370.

Research output: Contribution to journalArticle

Mavanji, V, Perez-Leighton, CE, Kotz, CM, Billington, CJ, Parthasarathy, S, Sinton, CM & Teske, JA 2015, 'Promotion of wakefulness and energy expenditure by orexin-a in the ventrolateral preoptic area', Sleep, vol. 38, no. 9, pp. 1361-1370. https://doi.org/10.5665/sleep.4970
Mavanji V, Perez-Leighton CE, Kotz CM, Billington CJ, Parthasarathy S, Sinton CM et al. Promotion of wakefulness and energy expenditure by orexin-a in the ventrolateral preoptic area. Sleep. 2015 Sep 1;38(9):1361-1370. https://doi.org/10.5665/sleep.4970
Mavanji, Vijayakumar ; Perez-Leighton, Claudio E. ; Kotz, Catherine M. ; Billington, Charles J. ; Parthasarathy, Sairam ; Sinton, Christopher M. ; Teske, Jennifer A. / Promotion of wakefulness and energy expenditure by orexin-a in the ventrolateral preoptic area. In: Sleep. 2015 ; Vol. 38, No. 9. pp. 1361-1370.
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