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1 Endocrine Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA
2 Veterans Affairs Medical Center, Minneapolis, Minnesota, USA; Minnesota Obesity Center, Minneapolis, Minnesota, USA; Departments of Food Science and Nutrition, University of Minnesota, Saint Paul, Minnesota, USA
3 Veterans Affairs Medical Center, Minneapolis, Minnesota, USA
4 Endocrine Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota, USA; Minnesota Obesity Center, Minneapolis, Minnesota, USA
* To whom correspondence should be addressed. E-mail: levine.james{at}mayo.edu.
In humans, nonexercise activity thermogenesis (NEAT) increases with positive energy balance. The mediator of the interaction between positive energy balance and physical activity is unknown. In this study, we address the hypothesis that orexin A acts in the hypothalamic paraventricular nucleus (PVN) to increase non-feeding associated physical activity. PVN-cannulated rats were injected with either orexin A or vehicle during the light and dark cycle. Spontaneous physical activity (SPA) was measured using arrays of infrared activity sensors and night-vision videotaped recording (VTR). Oxygen consumption and CO2 production were measured by indirect calorimetry. Feeding behavior was assessed by VTR. Regardless of the time point of injection, orexin A (1 nmol) was associated with dramatic increases in SPA for 2 hours after injection (orexin A; 6.27 ± 1.95 x 103 beam break count, n=24, vehicle; 1.85 ± 1.13 x 103, n=38. mean ± SD). This increase in SPA was accompanied by compatible increase in oxygen consumption. Duration of feeding was increased only when orexin A was injected in the early light phase and only accounted for 3.5 ± 2.5 % of the increased physical activity. In a dose-response experiment, increases in SPA were correlated with dose of orexin A linearly up to 2 nmol. PVN injections of the orexin receptor antagonist, SB-334867, were associated with decreases in SPA and attenuated the effects of PVN-injected orexin A. Thus orexin A can act in PVN to increase non-feeding associated physical activity, suggesting that this neuropeptide might be a mediator of NEAT.
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