Role of the locus coeruleus in enhanced orexin A-induced spontaneous physical activity in obesity-resistant rats

Jennifer A Teske, Claudio E. Perez-Leighton, Charles J. Billington, Catherine M. Kotz

Research output: Contribution to journalArticle

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Abstract

Orexin/hypocretin terminals innervate noradrenergic locus coeruleus (LC) neurons that project to the prefrontral cortex, which may influence spontaneous physical activity (SPA) and energy balance. Obesity-resistant (OR) rats have higher orexin receptors (OXR) mRNA in the LC and other brain regions, as well as lower adiposity compared with obese rats. These findings led us to hypothesize that orexin activity in the LC is relevant for the OR phenotype. We compared OR rats to Sprague-Dawley rats. We predicted that: 1) brain OXR expression pattern is sufficient to differentiate OR from non-bred Sprague-Dawley rats; 2) nonresting energy expenditure (NREE) and orexin A (OXA)-stimulated SPA after injection in LC would be greater in OR rats; and 3) the effect of OXA on SPA would be greater than its effect on feeding. OXR mRNA from 11 brain sites and the SPA and feeding responses to OXA in the LC were determined. Body composition, basal SPA, and EE were determined. Principal component analysis of the OXR expression pattern differentiates OR and Sprague-Dawley rats and suggests the OXR mRNA in the LC is important in defining the OR phenotype. Compared with Sprague-Dawley rats, OR rats had greater SPA and NREE and lower resting EE and adiposity. SPA responsivity to OXA in the LC was greater in OR rats compared with Sprague-Dawley rats. OXA in the LC did not stimulate feeding in OR or Sprague-Dawley rats. These data suggest that the LC is a prominent site modulating OXA-stimulated SPA, which promotes lower adiposity and higher nonresting EE.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume305
Issue number11
DOIs
StatePublished - Dec 1 2013

Fingerprint

Locus Coeruleus
Obesity
Orexin Receptors
Sprague Dawley Rats
Adiposity
Messenger RNA
Energy Metabolism
Brain
Orexins
Phenotype
Body Composition
Principal Component Analysis
Neurons
Injections

Keywords

  • Brain
  • Diet-induced obesity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Role of the locus coeruleus in enhanced orexin A-induced spontaneous physical activity in obesity-resistant rats. / Teske, Jennifer A; Perez-Leighton, Claudio E.; Billington, Charles J.; Kotz, Catherine M.

In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 305, No. 11, 01.12.2013.

Research output: Contribution to journalArticle

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