Agouti-related protein prevents self-starvation

• Published in: Molecular psychiatry Vol. 8; no. 2; pp. 235 - 240
• Main Authors: KAS, M. J. H, VAN DIJK, G, SCHEURINK, A. J. W, ADAN, R. A. H
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.02.2003
• Subjects: Adult and adolescent clinical studies; Agouti-Related Protein; Animals; Animals, Outbred Strains; Anorexia; Anorexia nervosa; Anorexia Nervosa - drug therapy; Anorexia Nervosa - metabolism; Biological and medical sciences; Body temperature; Brain; Caloric Restriction; Child clinical studies; Eating behavior disorders; Eating disorders; Exercise; Feeding Behavior - drug effects; Feeding Behavior - physiology; Female; Food; Food availability; Food intake; Gene Expression - drug effects; Hyperactivity; Hypothalamo-Hypophyseal System - metabolism; Hypothalamus; Hypothalamus (medial); Intercellular Signaling Peptides and Proteins; Medical sciences; Melanocortin receptors; Motor Activity - drug effects; Physical activity; Pituitary-Adrenal System - metabolism; Pro-Opiomelanocortin - genetics; Proteins; Proteins - metabolism; Proteins - pharmacology; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Rats; Rats, Wistar; Receptors, Corticotropin - metabolism; Receptors, Melanocortin; Starvation; Ventromedial Hypothalamic Nucleus - metabolism; Wheels; Physical exercise; Starvation; Pathophysiology; Rat; Hyperactivity; Body temperature; Rodentia; Etiopathogenesis; Exploration; Anorexia nervosa; Hypothalamus; Eating disorder; Experimental study; Melanocortin receptor; Vertebrata; Mammalia; Animal
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/sj.mp.4001206

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.