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Orexin A (hypocretin 1) injected into hypothalamic paraventricular nucleus and spontaneous physical activity in rats

¹Endocrine Research Unit, Mayo Clinic and Mayo Foundation, Rochester 55905; ²Veterans Affairs Medical Center and ³Minnesota Obesity Center, Minneapolis 55417; and ⁴Departments of Food Science and Nutrition, University of Minnesota, Saint Paul, Minnesota 55108

Submitted 24 March 2003 ; accepted in final form 21 November 2003

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 nonfeeding-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). O₂ 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 h after injection (orexin A: 6.27 ± 1.95 x 10³ beam break count, n = 24; vehicle: 1.85 ± 1.13 x 10³, n = 38). This increase in SPA was accompanied by compatible increase in O₂ consumption. Duration of feeding was increased only when orexin A was injected in the early light phase and accounted for only 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 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 nonfeeding-associated physical activity, suggesting that this neuropeptide might be a mediator of NEAT.

energy expenditure; hypothalamus; obesity; nonexercise activity thermogenesis

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