Decreased responsiveness to dietary fat in Otsuka Long-Evans Tokushima fatty rats lacking CCK-A receptors

Gary J. Schwartz, Andrew Whitney, Chris Skoglund, Thomas W. Castonguay, Timothy H. Moran

Research output: Contribution to journalArticlepeer-review

91 Scopus citations


Adult Otsuka Long-Evans Tokushima fatty (OLETF) rats lack functional cholecystokinin A (CCK-A) receptors, are diabetic, hyperphagic, and obese, and have patterns of ingestion consistent with a satiety deficit secondary to CCK insensitivity. Because dietary fat potently stimulates CCK release, we examined how dietary fat modulates feeding in adult male OLETF rats and their lean [Long-Evans Tokushima (LETO)] controls. High-fat feeding produced sustained overconsumption of high-fat diet (30% corn oil in powdered chow) over a 3-wk period in OLETF but not LETO rats. We then assessed the ability of gastric gavage (5 ml, 1-2 kcal/ml x 15 s) or duodenal preloads (1 kcal/ml, 0.44 ml/min x 10 min) of liquid carbohydrate (glucose), protein (peptone), or fat (Intralipid) to suppress subsequent 30-min 12.5% glucose intake in both strains. In OLETF rats, gastric and duodenal fat preloads were significantly less effective in suppressing subsequent intake than were equicaloric peptone or glucose. These results demonstrate that OLETF rats fail to compensate for fat calories and suggest that their hyperphagia and obesity may stem from a reduced ability to process nutrient-elicited gastrointestinal satiety signals.

Original languageEnglish (US)
Pages (from-to)R1144-R1151
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number4 46-4
StatePublished - Oct 1999
Externally publishedYes


  • Brain-gut communication
  • Energy homeostasis
  • Food intake
  • Non-insulin-dependent diabetes mellitus
  • Obesity

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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