Unraveling the obesity of OLETF rats.
Cholecystokinin (CCK) is a brain gut peptide that plays an important role in satiety. CCK inhibits food intake by reducing meal size. CCK's satiety actions are mediating through its interaction with CCK1 receptors. Otsuka Long Evans Tokushima Fatty (OLETF) rats are a CCK1 receptor knockout model that allows the study of multiple CCK functions. OLETF rats are hyperphagic with the hyperphagia expressed as a significant increase in the size of meals. OLETF rat obesity is secondary to the hyperphagia and has been proposed to derive from two regulatory deficits. One is secondary to the loss of a feedback satiety signal. The other results from increased dorsomedial hypothalamic NPY expression. Recent studies have examined developmental aspects of altered feeding, body weight and orexigenic signaling in OLETF rats. OLETF rats demonstrate increases in meal size in independent ingestion tests as early as two days of age. OLETF pups are also more efficient in suckling situations. Consistent with such developmental differences, examinations of patterns of hypothalamic gene expression in OLETF pups indicate significant increases in DMH NPY expression as early as postnatal day 15. Access to a running wheel and the resulting exercise have age dependent effects on OLETF food intake and obesity. With running wheel access shortly after weaning, food intake decreases to the levels of LETO controls. When running wheel access is discontinued, food intake temporarily increases resulting in an intermediate phenotype and the absence of diabetes. Together these data demonstrate roles for peripheral CCK and CCK in feeding and body weight control and support the use of the OLETF rat as a model for examining obesity development and for investigating how interventions at critical developmental time points can alter genetic influences on food intake and body weight.
Moran
Timothy H
TH
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Ross 618, 720 Rutland Ave, Baltimore, MD 21205, USA. tmoran@jhmi.edu
D000818:Animals; D002766:Cholecystokinin / Q000502:physiology; D004435:Eating / Q000502:physiology; D007031:Hypothalamus / Q000503:physiopathology; D009765:Obesity / Q000503:physiopathology*; D010805:Physical Conditioning, Animal / Q000502:physiology; D051381:Rats; D020334:Rats, Inbred OLETF / Q000502:physiology*; D043886:Receptor, Cholecystokinin A / Q000502:physiology
D043886:Receptor, Cholecystokinin A; D002766:Cholecystokinin