Amylin activates distributed CNS nuclei to control energy balance

• Amylin receptors are expressed in many energy balance-relevant nuclei.
• Amylin activates hindbrain, hypothalamic, and mesolimbic sites to control feeding.
• Amylin may be produced by structures other than the pancreas, including in the CNS.
• Amylin-based combination pharmacotherapies may be useful for treating obesity.

Amylin is a pancreas-derived neuropeptide that acts in the central nervous system (CNS) to reduce food intake. Much of the literature describing the anorectic effects of amylin are focused on amylin's actions in the area postrema, a hindbrain circumventricular structure. Although the area postrema is certainly an important site that mediates the intake-suppressive effects of amylin, several pieces of evidence indicate that amylin may also promote negative energy balance through action in additional CNS nuclei, including hypothalamic and mesolimbic structures. Therefore, this review highlights the distributed neural network mediating the feeding effects of amylin signaling with special attention being devoted to the recent discovery that the ventral tegmental area is physiologically relevant for amylin-mediated control of feeding. The production of amylin by alternative, extra-pancreatic sources and its potential relevance to food intake regulation is also considered. Finally, the utility of amylin and amylin-like compounds as a component of combination pharmacotherapies for the treatment of obesity is discussed.