Brainstem mechanisms of amylin-induced anorexia.
Amylin is secreted by pancreatic beta-cells and is believed to be a physiological signal of satiation. Amylin's effect on eating has been shown to be mediated via a direct action at the area postrema (AP) via amylin receptors that are heterodimers of the calcitonin receptor core protein with a receptor activity modifying protein. Peripheral amylin leads to accumulation of cyclic guanosine monophosphate, phosphorylated extracellular-signal regulated kinase 1/2 and c-Fos protein in AP neurons. The particular amylin-activated AP neurons mediating its anorexigenic action seem to be noradrenergic. The central pathways mediating amylin's effects have been characterized by lesioning and tracing studies, identifying important connections from the AP to the nucleus of the solitary tract and lateral parabrachial nucleus. Amylin was shown to interact, probably at the brainstem, with other signals involved in the short term control of food intake, namely cholecystokinin, glucagon-like peptide 1 and peptide YY. Amylin also interacts with the adiposity signal leptin; this interaction, which is thought to involve the hypothalamus, may have important implications for the development of new and improved hormonal obesity treatments. In conclusion, amylin actions on food intake seem to reside primarily within the brainstem, and the associated mechanisms are starting to be unraveled. The paper represents an invited review by a symposium, award winner or keynote speaker at the Society for the Study of Ingestive Behavior [SSIB] Annual Meeting in Portland, July 2009.
Institute of Veterinary Physiology and Zurich Center for Integrative Human Physiology, University of Zurich, 8057 Zurich, Switzerland. cpotes@vetphys.uzh.ch
Catarina Soares
CS
Potes
Thomas Alexander
TA
Lutz
D000682:Amyloid / Q000009:adverse effects*; D000818:Animals; D000855:Anorexia / Q000139:chemically induced*; D001067:Appetite Depressants / Q000009:adverse effects*; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D004435:Eating / Q000187:drug effects; D006801:Humans; D058228:Islet Amyloid Polypeptide; D009474:Neurons / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D000682:Amyloid; D001067:Appetite Depressants; D058228:Islet Amyloid Polypeptide