Independent feeding and metabolic actions of orexins in mice

Orexin-A and orexin-B (OX peptides) are two putative products of a newly di scovered secreted protein encoded by a mRNA restricted to neuronal cell bod ies of the lateral hypothalamus (LH). Because the activation of the LH can induce changes in energy balance, we wanted to investigate the actions of O X peptides on energy metabolism in mice. We injected male C57BL/6J mice wit h different doses (1, 3, and 10 nmol) of orexin-A and orexin-B into the thi rd ventricle (i3vt). A single i3vt injection of orexin-A 3 h into the light period slightly stimulated feeding at the lowest dose only over the follow ing 4 h (11 +/- 09 mg/mouse vs 80 +/- 13 mg/mouse, p < 0.05). Orexin-B show ed no effects at any dose. We therefore investigated the effects of 3 nmol orexin-A on energy utilization using indirect calorimetry. Single i3vt inje ction 3 h after light on, or just before dark onset, or in 4-h fasted mice resulted in increases in the metabolic rate. These effects were associated with decreases or increases in the respiratory quotient regarding the time of injection or the underlying metabolic state of the mice. The present fin dings provide direct evidence that OX peptides are more likely to be involv ed in the control of energy metabolism than of food intake in mice. (C) 199 8 Academic Press.