Behavioral responses to orexin, orexin receptor gene expression, and spontaneous physical activity contribute to individual sensitivity to obesity

There is significant variability in diet-induced obesity (DIO) among humans and rodents, which has been associated with differences in intrinsic spontaneous physical activity (SPA). The orexin neuropeptides positively modulate SPA through multiple brain sites, but the effects of DIO on orexin's...

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Bibliographic Details
Published in:American journal of physiology: endocrinology and metabolism 2012-10, Vol.303 (7), p.E865-E874
Main Authors: Perez-Leighton, Claudio E, Boland, Kelsey, Teske, Jennifer A, Billington, Charles, Kotz, Catherine M
Format: Article
Language:English
Subjects:
Animals
Brain
Diet, Fat-Restricted
Diet, High-Fat - adverse effects
Eating - drug effects
Gene Expression
Hypothalamic Area, Lateral - drug effects
Intracellular Signaling Peptides and Proteins - administration & dosage
Intracellular Signaling Peptides and Proteins - metabolism
Male
Motor Activity
Neuropeptides - administration & dosage
Neuropeptides - metabolism
Obesity
Obesity - genetics
Obesity - physiopathology
Orexin Receptors
Orexins
Peptides
Rats
Rats, Sprague-Dawley
Receptors, G-Protein-Coupled - genetics
Receptors, Neuropeptide - genetics
Rodents
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Summary:There is significant variability in diet-induced obesity (DIO) among humans and rodents, which has been associated with differences in intrinsic spontaneous physical activity (SPA). The orexin neuropeptides positively modulate SPA through multiple brain sites, but the effects of DIO on orexin's activity are not well understood. In this study, we tested the hypothesis that DIO sensitivity is mediated by decreased SPA and changes in the function of the orexins. As a DIO model, we used male Sprague-Dawley rats fed a high-fat (HF; 45% kcal from fat) or a low-fat (LF; 10% kcal from fat) diet for 10 wk. We measured SPA before and after HF or LF feeding and expression of orexin receptors by real-time PCR after dietary treatments. We tested DIO effects on orexin signaling by measuring SPA after injection of orexin A in the rostral lateral hypothalamus (RLH) before and after 10 wk of HF feeding. Finally, we tested whether daily orexin A RLH injections prevent DIO caused by HF feeding. Our results show that resistance to DIO is associated with an increase in SPA, SPA after injection of orexin A in RLH, and orexin receptor expression in sites that mediate orexin's effect on SPA, including RLH. We show that daily injections of orexin peptide in RLH prevent DIO without altering food intake. We estimate that the energetic cost of SPA after orexin A RLH injection accounts for approximately 61% of the extra caloric intake associated with HF intake, suggesting additional effects of orexins. In summary, our results suggest that variability in DIO sensitivity is mediated through adaptations in the activity of the orexin peptides and their receptors.
ISSN:0193-1849
1522-1555
DOI:10.1152/ajpendo.00119.2012