Orexins: New brain appetite stimulants Dan Gordon  Gastroenterology  Volume 114, Issue 5, (May 1998) DOI: 10.1016/S0016-5085(98)70301-4 Copyright © 1998 Terms and Conditions

Three pathways act in the hypothalamus to stimulate appetite directly, and one stimulates indirectly. Two related molecules, orexin A and orexin B, are produced mainly in the lateral hypothalamus and interact with two receptors known as OX1 and OX2. Fasting induces increased orexin mRNA and leptin decreases it. Previously known pathways involve neuropeptide Y in the arcuate nucleus and MCH in the lateral hypothalamus. These peptides interact with Y5 receptors and with presently uncharacterized MCH receptors respectively. The mRNAs for these peptides also are increased by fasting and inhibited by leptin. A fourth system that leads to increased appetite actually represents inhibition of an inhibitory pathway. This is the POMC > αMSH > MC4 receptor pathway. The activation of MC4 by αMSH inhibits appetite, and leptin stimulates this appetite inhibiting system. Agouti protein inhibits activation of the MC4 receptor, and animals in which agouti protein is missing have marked obesity. Ultimately all of the stimulatory pathways act on the paraventricular nucleus of the hypothalamus, but some also interact with the cerebral cortex. Stimulatory pathways are indicated by blue letters and solid blue arrows and inhibitory pathways by pink letters and dotted pink lines. Gastroenterology 1998 114, DOI: (10.1016/S0016-5085(98)70301-4) Copyright © 1998 Terms and Conditions