The anorectic hormone amylin contributes to feeding-related changes of neuronal activity in key structures of the gut-brain axis.
Amylin is a peptide hormone that is cosecreted with insulin from the pancreas during and after food intake. Peripherally injected amylin potently inhibits feeding by acting on the area postrema (AP), a circumventricular organ lacking a functional blood-brain barrier. We recently demonstrated that AP neurons are excited by a near physiological concentration of amylin. However, the subsequent neuronal mechanisms and the relevance of endogenously released amylin for the regulation of food intake are poorly understood. Therefore, we investigated 1) amylin's contribution to feeding-induced c-Fos expression in the rat AP and its ascending projection sites, and 2) amylin's ability to reverse fasting-induced c-Fos expression in the lateral hypothalamic area (LHA). Similar to amylin (20 microg/kg sc), refeeding of 24-h food-deprived rats induced c-Fos expression in the AP, the nucleus of the solitary tract, the lateral parabrachial nucleus, and the central nucleus of the amygdala. In AP-lesioned rats, the amylin-induced c-Fos expression in each of these sites was blunted, indicating an AP-mediated activation of these structures. Pretreatment with the amylin antagonist AC-187 (1 mg/kg sc) inhibited feeding-induced c-Fos expression in the AP. Food deprivation activated LHA neurons, a response known to be associated with hunger. This effect was reversed within 2 h after refeeding and also in nonrefed animals that received amylin. In summary, our data provide the first evidence that feeding-induced amylin release activates AP neurons projecting to subsequent relay stations known to transmit meal-related signals to the forebrain. Activation of this pathway seems to coincide with an inhibition of LHA neurons.
Riediger
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Institute of Veterinary Physiology, University of Zurich, 8057 Zurich, Switzerland. triedig@vetphys.unizh.ch
Zuend
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Becskei
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Lutz
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D000682:Amyloid / Q000494:pharmacology / Q000502:physiology*; D000821:Animal Feed; D000818:Animals; D031608:Area Postrema / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000502:physiology*; D004435:Eating / Q000502:physiology*; D005508:Food Deprivation / Q000502:physiology; D007026:Hypothalamic Area, Lateral / Q000378:metabolism; D007150:Immunohistochemistry; D007422:Intestines / Q000294:innervation*; D058228:Islet Amyloid Polypeptide; D008297:Male; D009420:Nervous System / Q000166:cytology; D009424:Nervous System Physiological Phenomena; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000682:Amyloid; D058228:Islet Amyloid Polypeptide; D016760:Proto-Oncogene Proteins c-fos