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This Article Full Text Full Text (PDF) All Versions of this Article: 583/2/487    most recent jphysiol.2007.138867v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cottone, P. Articles by Zorrilla, E. P. Search for Related Content PubMed PubMed Citation Articles by Cottone, P. Articles by Zorrilla, E. P. Related Collections Neuroscience

¹ Committee on the Neurobiology of Addictive Disorders (CNAD)
² Harold L. Dorris Neurological Research Institute, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA
³ Department of Nutrition Sciences, Clinical Nutrition Research Center, University of Alabama at Birmingham, Birmingham, AL, USA
⁴ Department of Psychology, College of Liberal Arts and Sciences, Wayne State University, Detroit, MI 48202, USA

With one billion people overweight worldwide, the need to identify risk factors and treatments for obesity is urgent. The present study determined whether rats genetically prone to diet-induced obesity (DIO) show preexisting differences in meal microstructure and are sensitive to central anorectic effects of corticotropin-releasing factor type 2 (CRF₂) receptor stimulation. Male, selectively bred DIO rats and their diet resistant (DR) counterparts (n = 9/genotype) were weaned onto low-fat chow and compared as young adults for spontaneous or intracerebroventricular urocortin 2 administration-induced (0, 0.3, 1, 3 µg) differences in ingestion. DIO rats were hyperphagic selectively at the dark cycle onset, showing shorter latencies to initiate feeding, faster returns to eating following meal completion, and a lower satiety ratio than DR rats. At other times, DIO rats had briefer postmeal intervals, but ate smaller and briefer meals, resulting in normal intake. DIO rats also ate faster than DR rats. Urocortin 2 was less potent in DIO rats, ineffective at the 0.3 µg dose, but produced CRF₂ antagonist-reversible anorexia at higher doses. Though heavier, chow-maintained DIO rats were proportionately as or more lean than DR rats. Thus, DIO rats showed signs of a preexisting, heritable deficit in the maintenance of postmeal satiety and a reduced sensitivity to anorectic CRF₂ agonist stimulation. The meal patterns of DIO rats temporally resemble human ‘snacking’ behaviour, which predicts adult obesity. Because central CRF₂ stimulation retains full anorectic efficacy at higher doses in the DIO model, manipulating this neuropeptidergic system might yield new therapeutic approaches for diet-induced obesity.

(Received 18 June 2007; accepted after revision 6 July 2007; first published online 12 July 2007)
Corresponding author P. Cottone or E.P. Zorrilla: Committee on the Neurobiology of Addictive Disorders, SP30-2400, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA. Email: cottone{at}scripps.edu or ezorrilla{at}scripps.edu

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