Agouti-related protein prevents self-starvation.
Food restriction leads to a paradoxical increase in physical activity and further suppression of food intake, such as observed in anorexia nervosa.(1,2) To understand this pathophysiological process, we induced physical hyperactivity and self-starvation in rats by restricting food in the presence of running wheels. Normally, decreased melanocortin receptor activity will prevent starvation.(3,4) However, we found that self-starvation increased melanocortin receptors in the ventral medial hypothalamus, a brain region involved in eating behavior.(5) Suppression of melanocortin receptor activity, via central infusion of Agouti-related protein (AgRP), increased survival rate in these rats by counteracting physical hyperactivity, food intake suppression as well as deregulated body temperature. We conclude that self-starvation may result from insufficient suppression of central melanocortin receptor activity.
Kas
M J H
MJ
Department of Medical Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
van Dijk
G
G
Scheurink
A J W
AJ
Adan
R A H
RA
D054369:Agouti-Related Protein; D000818:Animals; D021461:Animals, Outbred Strains; D000856:Anorexia Nervosa / Q000188:drug therapy* / Q000378:metabolism*; D031204:Caloric Restriction; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D009043:Motor Activity / Q000187:drug effects*; D010913:Pituitary-Adrenal System / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000235:genetics; D011506:Proteins / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018043:Receptors, Corticotropin / Q000378:metabolism; D044101:Receptors, Melanocortin; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism
C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D036341:Intercellular Signaling Peptides and Proteins; D011506:Proteins; D018043:Receptors, Corticotropin; D044101:Receptors, Melanocortin; D011333:Pro-Opiomelanocortin