title: Centrally administered urocortin 2 decreases gorging on high-fat diet in both diet-induced obesity-prone and -resistant rats.
abstract: OBJECTIVE
  Obesity is a costly, deadly public health problem for which new treatments are needed. Individual differences in meal pattern have been proposed to have a role in obesity risk. The present study tested the hypothesis that (i) the microstructure of chronic high-fat diet intake differs between genetically selected diet-induced obesity (DIO) and diet-resistant (DR) rats, and (ii) central administration of urocortin 2 (Ucn 2), a corticotropin-releasing factor type 2 agonist, decreases high-fat diet intake not only in lean DR rats, but also in obese DIO rats.
  
  
  METHODS
  Male, selectively bred DIO and DR rats (n=10/genotype) were chronically fed a high-fat diet. Food and water intake as well as ingestion microstructure were then compared under baseline conditions and following third intracerebroventricular injection of Ucn 2 (0, 0.1, 0.3, 1, 3 μg).
  
  
  RESULTS
  Irrespective of genotype, Ucn 2 reduced nocturnal food intake with a minimum effective dose of 0.3 μg, suppressing high-fat diet intake by ∼40% at the 3 μg dose. Ucn 2 also made rats of both genotypes eat smaller and briefer meals, including at doses that did not reduce drinking. Obese DIO rats ate fewer but larger meals than DR rats, which they ate more quickly and consumed with two-third less water.
  
  
  CONCLUSIONS
  Unlike leptin and insulin, Ucn 2 retains its full central anorectic efficacy to reduce high-fat diet intake even in obese, genetically prone DIO rats, which otherwise show a 'gorging' meal pattern. These results open new opportunities of investigation toward treating some forms of DIO.
authors.affiliation: 1] Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA [2] Laboratory of Addictive Disorders, Departments of Pharmacology and Psychiatry, Boston University School of Medicine, Boston, MA, USA [3] Harold L. Dorris Neurological Research Institute, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: P
authors.initials: P
authors.lastname: Cottone
authors.forename: V
authors.initials: V
authors.lastname: Sabino
authors.forename: T R
authors.initials: TR
authors.lastname: Nagy
authors.forename: D V
authors.initials: DV
authors.lastname: Coscina
authors.forename: B E
authors.initials: BE
authors.lastname: Levin
authors.forename: E P
authors.initials: EP
authors.lastname: Zorrilla
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects; D001522:Behavior, Animal; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D051381:Rats; D011922:Rats, Mutant Strains; D013997:Time Factors; D054832:Urocortins / Q000494:pharmacology*
chemical_list: D001067:Appetite Depressants; D004041:Dietary Fats; D054832:Urocortins