AgRP(83-132) and SHU9119 differently affect activity-based anorexia.
Activity-based anorexia (ABA) mimics starvation and hyperactivity of anorexia nervosa patients in rats. Activation of the melanocortin (MC) system leads to hypophagia and increased energy expenditure in ad libitum fed rats. Therefore, activation of the MC system might underlie the development and propagation of ABA. Pro-opiomelanocortin (POMC) gene expression is normally decreased during negative energy balance. Strikingly, we found a transient up-regulation of POMC mRNA levels in the arcuate nucleus during the development of ABA, indicating a hyperactive MC system. However, wheel running and food intake were not influenced by treating ABA rats with the competitive antagonist SHU9119. This suggests that agonism of MC receptors by endogenous alpha-melanocyte-stimulating hormone (alpha-MSH) levels does not underlie ABA. Instead, treatment with the inverse agonist AgRP(83-132) did ameliorate signs of ABA. This implies that modulation of constitutive MC receptor activity rather than antagonizing putative alpha-MSH release contributes to the development and propagation of ABA.
Hillebrand
Jacquelien J G
JJ
Department of Pharmacology and Anatomy, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
Kas
Martien J H
MJ
Scheurink
Anton J W
AJ
van Dijk
Gertjan
G
Adan
Roger A H
RA
D054369:Agouti-Related Protein; D000818:Animals; D000855:Anorexia / Q000188:drug therapy* / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology / Q000627:therapeutic use*; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use*; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D044101:Receptors, Melanocortin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism
D054369:Agouti-Related Protein; D010446:Peptide Fragments; D044101:Receptors, Melanocortin; C411703:agouti-related protein-(83-132); C103272:SHU 9119; D011333:Pro-Opiomelanocortin; D009074:Melanocyte-Stimulating Hormones