Orexins, feeding, and energy balance.

In this chapter, we give an overview of the current status of the role of orexins in feeding and energy homeostasis. Orexins, also known as hypocretins, initially were discovered in 1998 as hypothalamic regulators of food intake. A little later, their far more important function as regulators of sleep and arousal came to light. Despite their restricted distribution, orexin neurons have projections throughout the entire brain, with dense projections especially to the paraventricular nucleus of the thalamus, the arcuate nucleus of the hypothalamus, and the locus coeruleus and tuberomammillary nucleus. Its two receptors are orexin receptor 1 and orexin receptor 2. These receptors show a specific and localized distribution in a number of brain regions, and a variety of different actions has been demonstrated upon their binding. Our group showed that through the autonomic nervous system, the orexin system plays a key role in the control of glucose metabolism, but it has also been shown to stimulate sympathetic outflow, to increase body temperature, heart rate, blood pressure, and renal sympathetic nerve activity. The well-known effects of orexin on the control of food intake, arousal, and wakefulness appear to be more extensive than originally thought, with additional effects on the autonomic nervous system, that is, to increase body temperature and energy metabolism.