Functions of orexins in peripheral tissues

Orexin A (OXA) and orexin B were originally isolated as hypothalamic peptides regulating sleep, wakefulness and feeding. However, growing evidence suggests that orexins have major functions also in the peripheral tissues. Central orexigenic pathways originating from medulla activate the hypothalamus-pituitary axis and can influence the sympathetic tone. Orexins and their receptors are widely dispersed throughout the intestine, where orexin receptors are regulated by the nutritional status, affect insulin secretion and intestinal motility. Although the primary source of the peptide has not been elucidated, OXA is detected in plasma and its level varies in response to the metabolic state. In this review, we focus on the current knowledge on peripheral functions of orexins and discuss possible endocrine, paracrine and neurocrine roles.