Circulating GLP-1 and CCK-8 reduce food intake by capsaicin-insensitive, nonvagal mechanisms.
Previous reports suggest that glucagon-like peptide (GLP-1), a peptide secreted from the distal small intestine, is an endocrine satiation signal. Nevertheless, there are conflicting reports regarding the site where circulating GLP-1 acts to reduce food intake. To test the hypothesis that vagal afferents are necessary for reduction of food intake by circulating GLP-1, we measured intake of 15% sucrose during intravenous GLP-1 infusion in intact, vagotomized, and capsaicin-treated rats. We also measured sucrose intake during intravenous infusion of cholecystokinin, a peptide known to reduce food intake via abdominal vagal afferents. We found that reduction of intake by GLP-1 was not diminished by capsaicin treatment or vagotomy. In fact, reduction of sucrose intake by our highest GLP-1 dose was enhanced in vagotomized and capsaicin-treated rats. Intravenous GLP-1 induced comparable increases of hindbrain c-Fos immunoreactivity in intact, capsaicin-treated, and vagotomized rats. Plasma concentrations of active GLP-1 in capsaicin-treated rats did not differ from those of controls during the intravenous infusions. Finally, capsaicin treatment was not associated with altered GLP-1R mRNA in the brain, but nodose ganglia GLP-1R mRNA was significantly reduced in capsaicin-treated rats. Although reduction of food intake by intraperitoneal cholecystokinin was abolished in vagotomized and capsaicin-treated rats, reduction of intake by intravenous cholecystokinin was only partially attenuated. These results indicate that vagal or capsaicin-sensitive neurons are not necessary for reduction of food intake by circulating (endocrine) GLP-1, or cholecystokinin. Vagal participation in satiation by these peptides may be limited to paracrine effects exerted near the sites of their secretion.
Programs in Neuroscience and Dept. of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State Univ., Pullman, WA 99164-6520, USA.
Jingchuan
J
Zhang
Robert C
RC
Ritter
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000494:pharmacology*; D008297:Male; D009620:Nodose Ganglion / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012844:Sincalide / Q000097:blood / Q000494:pharmacology*; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D052216:Glucagon-Like Peptide 1; D012844:Sincalide; D002211:Capsaicin