Corticotropin-releasing factor-overexpressing mice exhibit reduced neuronal activation in the arcuate nucleus and food intake in response to fasting.
Corticotropin-releasing factor (CRF) overexpressing (OE) mice are a genetic model that exhibits features of chronic stress. We investigated whether the adaptive feeding response to a hypocaloric challenge induced by food deprivation is impaired under conditions of chronic CRF overproduction. Food intake response to a 16-h overnight fast and ip injection of gut hormones regulating food intake were compared in CRF-OE and wild type (WT) littermate mice along with brain Fos expression, circulating ghrelin levels, and gastric emptying of a nonnutrient meal. CRF-OE mice injected ip with saline showed a 47 and 44% reduction of 30-min and 4-h cumulative food intake response to an overnight fast, respectively, compared with WT. However, the 30-min food intake decrease induced by ip cholecystokinin (3 microg/kg) and increase by ghrelin (300 microg/kg) were similar in CRF-OE and WT mice. Overnight fasting increased the plasma total ghrelin to similar levels in CRF-OE and WT mice, although CRF-OE mice had a 2-fold reduction of nonfasting ghrelin levels. The number of Fos-immunoreactive cells induced by fasting in the arcuate nucleus was reduced by 5.9-fold in CRF-OE compared with WT mice whereas no significant changes were observed in other hypothalamic nuclei. In contrast, fasted CRF-OE mice displayed a 5.6-fold increase in Fos-immunoreactive cell number in the dorsal motor nucleus of the vagus nerve and a 34% increase in 20-min gastric emptying. These findings indicate that sustained overproduction of hypothalamic CRF in mice interferes with fasting-induced activation of arcuate nucleus neurons and the related hyperphagic response.
Stengel
Andreas
A
Center for Ulcer Research and Education, Digestive Diseases Research Center, Digestive Diseases Division, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90073, USA.
Goebel
Miriam
M
Million
Mulugeta
M
Stenzel-Poore
Mary P
MP
Kobelt
Peter
P
Mönnikes
Hubert
H
Taché
Yvette
Y
Wang
Lixin
L
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects / Q000502:physiology*; D002766:Cholecystokinin / Q000494:pharmacology; D003346:Corticotropin-Releasing Hormone / Q000235:genetics*; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D002149:Energy Intake / Q000187:drug effects; D005215:Fasting / Q000502:physiology*; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation; D016762:Genes, fos; D054439:Ghrelin / Q000494:pharmacology; D006963:Hyperphagia / Q000503:physiopathology; D007033:Hypothalamus, Middle / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009474:Neurons / Q000502:physiology*; D018697:Nootropic Agents / Q000494:pharmacology; D012844:Sincalide / Q000031:analogs & derivatives / Q000494:pharmacology
C090019:8-sulfocholecystokinin octapeptide; D054439:Ghrelin; D018697:Nootropic Agents; D002766:Cholecystokinin; D003346:Corticotropin-Releasing Hormone; D012844:Sincalide
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