Feeding microstructure in diet-induced obesity susceptible versus resistant rats: central effects of urocortin 2.
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 (CRF(2)) 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 microg) 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 microg dose, but produced CRF(2) 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 CRF(2) agonist stimulation. The meal patterns of DIO rats temporally resemble human 'snacking' behaviour, which predicts adult obesity. Because central CRF(2) 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.
Cottone
Pietro
P
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA. cottone@scripps.edu or ezorrilla@scripps.edu
Sabino
Valentina
V
Nagy
Tim R
TR
Coscina
Donald V
DV
Zorrilla
Eric P
EP
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D001823:Body Composition; D001835:Body Weight; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D004032:Diet / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004326:Drinking; D005247:Feeding Behavior / Q000187:drug effects; D005838:Genotype; D006963:Hyperphagia / Q000209:etiology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D010641:Phenotype; D051381:Rats; D011922:Rats, Mutant Strains; D018019:Receptors, Corticotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D054832:Urocortins / Q000008:administration & dosage / Q000378:metabolism*
D001067:Appetite Depressants; C101531:CRF receptor type 2; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D054832:Urocortins; C120841:astressin B; D003346:Corticotropin-Releasing Hormone