The other side of the orexins: endocrine and metabolic actions

Although it is clear that the orexin/hypocretin peptides have a significant, physiologically relevant role in sleep/wakefulness, a broader picture has emerged indicating metabolic actions that may depend upon both neural and endocrine mechanisms for their manifestation. The ability of exogenous peptide to activate sympathetic tone, increase locomotor activity, and alter feeding behavior, together with the observed alterations in those functions in knockout animals, strongly suggests important neural actions of the endogenous orexins/hypocretins. Likewise, the action of exogenously administered peptides to alter endocrine function, in particular corticotropin release, has now been mirrored by potential endocrinopathies in knockout animals. Thus these pluripotent peptides hold great potential not only for the treatment of human narcolepsy but also to provide insight into the coordinated regulation of multiple physiological systems.