title: Decreased intestinal nutrient response in diet-induced obese rats: role of gut peptides and nutrient receptors.
abstract: OBJECTIVE
  Diet-induced obesity (DIO) is an excellent model for examining human obesity comprising both genotypic and environmental (diet) factors. Decreased responsiveness to peripheral satiety signaling may be responsible for the hyperphagia in this model. In this study, we investigated responses to nutrient-induced satiation in outbred DIO and DIO-resistant (DR) rats fed a high-energy/high-fat (HE/HF) diet as well as intestinal satiety peptide content, intestinal nutrient-responsive receptor abundance and vagal anorectic receptor expression.
  
  
  METHODS
  Outbred DIO and DR rats fed a HE/HF diet were tested for short-term feeding responses following nutrient (glucose and intralipid (IL)) gastric loads. Gene and protein expressions of intestinal satiety peptides and fatty acid-responsive receptors were examined from isolated proximal intestinal epithelial cells and cholecystokinin-1 receptor (CCK-1R) and leptin receptor (LepR) mRNA from the nodose ganglia of DIO and DR animals.
  
  
  RESULTS
  DIO rats were less responsive to IL- (P<0.05) but not glucose-induced suppression of food intake compared with DR rats. DIO rats exhibited decreased CCK, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1; P<0.05 for each) protein expression compared with DR rats. Also, DIO rats expressed more G-protein-coupled receptor 40 (GPR40; P<0.0001), GPR41 (P<0.001) and GPR120 (P<0.01) relative to DR rats. Finally, there were no differences in mRNA expression for CCK-1R and LepR in the nodose ganglia of DIO and DR rats.
  
  
  CONCLUSIONS
  Development of DIO may be partly due to decreased fat-induced satiation through low levels of endogenous satiety peptides, and changes in intestinal nutrient receptors.
authors.affiliation: INRA, Centre de Recherche de Jouy-en-Josas, UMR 1319, MICALIS, Neurobiology of Ingestive Behavior, Domaine de Vilvert, Jouy-en-Josas, France.
authors.forename: F A
authors.initials: FA
authors.lastname: Duca
authors.forename: T D
authors.initials: TD
authors.lastname: Swartz
authors.forename: Y
authors.initials: Y
authors.lastname: Sakar
authors.forename: M
authors.initials: M
authors.lastname: Covasa
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004435:Eating; D002149:Energy Intake; D019858:Enteroendocrine Cells / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D041981:Gastrointestinal Tract / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012527:Satiation; D011984:Sensory Receptor Cells / Q000378:metabolism*; D015398:Signal Transduction