Food deprivation differentially modulates orexin receptor expression and signaling in rat hypothalamus and adrenal cortex

1 Biomedical Research Institute, Department of Biological Sciences, 2 Warwick Medical School, University of Warwick, Coventry; and 3 The Dean's Office, The Medical School, University of Leeds, Leeds, United Kingdom Submitted 2 August 2004 ; accepted in final form 10 January 2005 Although starva...

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Published in:American journal of physiology: endocrinology and metabolism 2005-06, Vol.288 (6), p.E1089-E1100
Main Authors: Karteris, Emmanouil, Machado, Rachel J, Chen, Jing, Zervou, Sevasti, Hillhouse, Edward W, Randeva, Harpal S
Format: Article
Language:English
Subjects:
Adrenal Cortex - metabolism
Animals
Blotting, Western
Cholera Toxin - metabolism
Corticosterone - blood
Food Deprivation - physiology
Gene Expression Regulation - physiology
GTP-Binding Proteins - metabolism
Hypothalamo-Hypophyseal System - metabolism
Hypothalamus - metabolism
Male
Orexin Receptors
Pertussis Toxin - metabolism
Pituitary-Adrenal System - metabolism
Random Allocation
Rats
Rats, Wistar
Receptors, G-Protein-Coupled
Receptors, Neuropeptide - biosynthesis
Receptors, Neuropeptide - genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Signal Transduction - physiology
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Summary:1 Biomedical Research Institute, Department of Biological Sciences, 2 Warwick Medical School, University of Warwick, Coventry; and 3 The Dean's Office, The Medical School, University of Leeds, Leeds, United Kingdom Submitted 2 August 2004 ; accepted in final form 10 January 2005 Although starvation-induced biochemical and metabolic changes are perceived by the hypothalamus, the adrenal gland plays a key role in the integration of metabolic activity and energy balance, implicating feeding as a major synchronizer of rhythms in the hypothalamic-pituitary-adrenal (HPA) axis. Given that orexins are involved in regulating food intake and activating the HPA axis, we hypothesized that food deprivation, an acute challenge to the systems that regulate energy balance, should elicit changes in orexin receptor signaling at the hypothalamic and adrenal levels. Food deprivation induced orexin type 1 (OX1R) and 2 (OX2R) receptors at mRNA and protein levels in the hypothalamus, in addition to a fivefold increase in prepro-orexin mRNA. Cleaved peptides OR-A and OR-B are also elevated at the protein level. Interestingly, adrenal OX1R and OX2R levels were significantly reduced in food-deprived animals, whereas there was no expression of prepro-orexin in the adrenal gland in either state. Food deprivation exerted a differential effect on OXR-G protein coupling. In the hypothalamus of food deprived rats compared with controls, a significant increase in coupling of orexin receptors to G q , G s , and G o was demonstrated, whereas coupling to G i was relatively less. However, in the adrenal cortex of the food-deprived animal, there was decreased coupling of orexin receptors to G s , G o , and G q and increased coupling to G i . Subsequent second-messenger studies (cAMP/IP 3 ) have supported these findings. Our data indicate that food deprivation has differential effects on orexin receptor expression and their signaling characteristics at the hypothalamic and adrenocortical levels. These findings suggest orexins as potential metabolic regulators within the HPA axis both centrally and peripherally. Address for reprint requests and other correspondence: E. Karteris, Biomedical Research Institute, Univ. of Warwick, Gibbet Hill Rd., Coventry CV4 7AL, UK (E-mail: e.k.karteris{at}warwick.ac.uk )
ISSN:0193-1849
1522-1555
DOI:10.1152/ajpendo.00351.2004