Hyperphagia and obesity of OLETF rats lacking CCK1 receptors: developmental aspects.
Otsuka Long Evans Tokushima Fatty (OLETF) rats have a deletion in the gene encoding the cholecystokinin-1 (CCK1) receptor. This deletion prevents protein expression, making the OLETF rat a CCK1 receptor knockout model. Consistent with the absence of CCK1 receptors, OLETF rats do not reduce their food intake in response to exogenously administered CCK and consume larger than normal meals. This deficit in within-meal feedback signaling is evident in liquid as well as solid meals. Neonatal OLETF rats show similar differences in independent ingestion tests. Intake is higher and is reflected in greater licking behavior. Neonatal OLETF rats also have diminished latencies to consume and higher initial ingestion rats. Adult OLETF rats are hyperphagic and obese. Although arcuate nucleus peptide gene expression is apparently normal in OLETF rats, when obesity is prevented through pair-feeding to amounts consumed by control Long Evans Tokushima Otsuka (LETO) rats, dorsomedial hypothalamic NPY mRNA expression is significantly elevated in OLETF rats. NPY overexpression is also evident in preobese, juvenile OLETF rats suggesting a causal role for this overexpression in the hyperphagia and obesity. Running wheel exercise normalizes food intake and body weight in OLETF rats. When access to exercise is provided at a time when OLETF rats are obese, the effects are limited to the period of exercise. When running wheel access is available to younger, preobese OLETF rats, exercise results in long lasting reductions in food intake and body weight and improved glucose regulation. These lasting metabolic effects of exercise may be secondary to an exercise induced reduction in DMH NPY mRNA expression.
Moran
Timothy H
TH
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. tmoran@jhmi.edu
Bi
Sheng
S
D000818:Animals; D002766:Cholecystokinin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002149:Energy Intake; D005247:Feeding Behavior; D017353:Gene Deletion; D006963:Hyperphagia / Q000235:genetics* / Q000378:metabolism; D020645:Mediodorsal Thalamic Nucleus / Q000378:metabolism; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D020334:Rats, Inbred OLETF; D011949:Receptors, Cholecystokinin / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin