title: Urocortin I inhibits the effects of ghrelin and neuropeptide Y on feeding and energy substrate utilization.
abstract: The corticotropin releasing hormone-related ligand, urocortin-I (UcnI), suppresses food intake when injected into multiple hypothalamic and extrahypothalamic areas. UcnI also alters energy substrate utilization, specifically via enhanced fat oxidation as reflected in reductions in respiratory quotient (RQ). In the present study we compared the feeding and metabolic effects of ghrelin and NPY following pretreatment with UcnI. Direct PVN injections of NPY (50 pmol) and ghrelin (50 pmol) were orexigenic while UcnI (10-40 pmol) reliably suppressed food intake. Both ghrelin and NPY increased RQ, indicating enhanced utilization of carbohydrates and the preservation of fat stores. UcnI alone suppressed RQ responses. PVN UcnI attenuated the effects of both ghrelin and NPY on food intake and energy substrate utilization. While ghrelin (5 pmol) potentiated the effect of NPY (25 pmol) on RQ and food intake, these responses were inhibited by pretreatment with UcnI (10 pmol). In conclusion, PVN NPY and ghrelin stimulate eating and promote carbohydrate oxidation while inhibiting fat utilization. These effects are blocked by UcnI which alone suppresses appetite and promotes fat oxidation. Overall these findings are consistent with a possible interactive role of PVN NPY, ghrelin and urocortin in the modulation of appetite and energy metabolism.
authors.affiliation: Department of Psychology, Reed College, 3203 SE Woodstock Blvd, Portland, OR 97202, USA. pcurrie@reed.edu
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Currie
authors.forename: Christine D
authors.initials: CD
authors.lastname: Coiro
authors.forename: Raya
authors.initials: R
authors.lastname: Duenas
authors.forename: Janet L
authors.initials: JL
authors.lastname: Guss
authors.forename: Aaisha
authors.initials: A
authors.lastname: Mirza
authors.forename: Neta
authors.initials: N
authors.lastname: Tal
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology; D004435:Eating / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology; D054439:Ghrelin / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D008297:Male; D009478:Neuropeptide Y / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism / Q000502:physiology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D054832:Urocortins / Q000502:physiology*
chemical_list: D001067:Appetite Depressants; D054439:Ghrelin; D009478:Neuropeptide Y; D054832:Urocortins