Procalcitonin N-terminal peptide causes catabolic effects via the hypothalamus and prostaglandin-dependent pathways.
Recent evidence suggests that the free amino-terminal fragment of procalcitonin (N-PCT) plays a role in the central control of feeding behavior and energy homeostasis. However, little is known about the mechanisms through which N-PCT works. Here we report that intracerebroventricular administration of N-PCT to free-feeding male rats induced a significant decrease of longer-term food intake and body weight gain. Conversely, N-PCT increased body temperature. We also show that intracerebroventricular administration of N-PCT induced a marked neuronal activation in key thermoregulatory and feeding areas of the hypothalamus. We further show that N-PCT increases the responsiveness of proopiomelanocortin anorexigenic neurons in the arcuate nucleus of the hypothalamus, and that stimulation of the de novo synthesis of prostaglandins is crucial for the central effects induced by N-PCT. Results support the role of N-PCT to the central control of feeding behavior and suggest that N-PCT, acting probably through the eicosanoid cyclooxygenase pathway, may act as a signaling molecule in the hypothalamus by regulating the activity of anorexigenic neurons in the hypothalamus.
Tavares
Eva
E
Experimental and Clinical Pharmacology Research Unit, Valme University Hospital, Faculty of Medicine, University of Sevilla, Sevilla, Spain.
Miñano
Francisco J
FJ
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D002116:Calcitonin / Q000008:administration & dosage / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide; D004734:Energy Metabolism / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D007031:Hypothalamus / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism*; D011498:Protein Precursors / Q000008:administration & dosage / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
C000606591:Calca protein, rat; D010446:Peptide Fragments; D011453:Prostaglandins; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D011333:Pro-Opiomelanocortin; D002116:Calcitonin; D011451:Prostaglandin-Endoperoxide Synthases; D015740:Calcitonin Gene-Related Peptide