title: Impaired GLP-1 signaling contributes to reduced sensitivity to duodenal nutrients in obesity-prone rats during high-fat feeding.
abstract: OBJECTIVE
  Increased consumption of a high-fat (HF) diet is a salient contributor to obesity; however, how diminished satiation signaling contributes to overconsumption and obesity development remains poorly understood.
  
  
  METHODS
  Using obese-prone (OP) and obese-resistant (OR) rats, we tested feeding responses to intragastric liquid meal replacement, prior and after HF feeding. Next, chow- and HF-fed OP and OR rats were tested for sensitivity to intraduodenal glucose, intralipid, and meal replacement loads. To examine the role of glucagon-like peptide-1 (GLP-1) and vagal signaling, animals were treated with exendin-9, GLP-1 receptor antagonist, prior to meal replacement infusion, and Fos-like immunoreactivity (Fos-Li) in the dorsal hindbrain was examined after infusion.
  
  
  RESULTS
  OP and OR rats reduced chow intake equally following gastric liquid meal; however, after 2 weeks of HF feeding, intragastric meal replacement reduced food intake less in OP than OR. Similarly, HF feeding, but not chow, diminished the suppressive effects of intraduodenal meal replacement, glucose, and intralipid in OP compared to OR. This effect was associated with lower Fos-Li expression in the dorsal hindbrain of OP rats. Finally, exendin-9 failed to attenuate reduction of food intake by meal replacement in OP rats during HF feeding.
  
  
  CONCLUSIONS
  Susceptibility to obesity coupled with HF feeding results in rapid impairments in nutrient-induced satiation through blunted responses in endogenous GLP-1 and hindbrain vagal afferent signaling.
authors.affiliation: Toronto General Research Institute and Department of Medicine, University Health Network, Toronto, Ontario, Canada.
authors.forename: Frank A
authors.initials: FA
authors.lastname: Duca
authors.affiliation: College of Dental Medicine, Western University of the Health Sciences, Pomona, California, USA.
authors.forename: Shahbaz
authors.initials: S
authors.lastname: Katebzadeh
authors.affiliation: College of Osteopathic Medicine, Department of Basic Medical Sciences, Western University of the Health Sciences, Pomona, California, USA.|Department of Health and Human Development, University "Stefan Cel Mare" Suceava, Suceava, Romania.
authors.forename: Mihai
authors.initials: M
authors.lastname: Covasa
mesh_terms: D000818:Animals; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000494:pharmacology; D004198:Disease Susceptibility; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D004435:Eating / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000378:metabolism*; D051381:Rats; D012527:Satiation / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology
chemical_list: D004041:Dietary Fats; D052216:Glucagon-Like Peptide 1