Gastric distension induces c-Fos in medullary GLP-1/2-containing neurons.
A group of neurons in the caudal nucleus of the solitary tract (NTS) processes preproglucagon to glucagon-like peptides (GLP)-1 and -2, peptides that inhibit food intake when administered intracerebroventricularly. The GLP-1/2-containing neural pathways have been suggested to play a role in taste aversion and nausea because LiCl activates these neurons, and LiCl-induced suppression of food intake can be blocked by the GLP-1 receptor antagonist exendin-9. As many gastrointestinal signals related to both satiety and nausea/illness travel via the vagus nerve to the caudal medulla, the present study assessed the capacity of different types of gastric distension (a purely mechanical stimulus) to activate GLP-1 neurons in the caudal NTS. Gastric balloon distension (1.4 ml/min first 5 min, 0.4 ml/min next 5 min, 9 ml total, held for 60 min) in nonanesthetized, freely moving rats produced 12- and 17-fold increases in c-Fos-expressing NTS neurons when distension was mainly in the fundus or corpus, respectively. Fundus and corpus distension increased the percentage of c-Fos-activated GLP-1 neurons to 21 +/- 9% and 32 +/- 5% compared with 1 +/- 1% with sham distension (P < 0.01). Thus gastric distension that may be considered within the physiological range activates GLP-1/2-containing neurons, suggesting some role in normal satiety. The results support the view that the medullary GLP system is involved in appetite control and is activated by stimuli within the behavioral continuum, ranging from satiety to nausea.
Vrang
Niels
N
Rheoscience, 2610 Rødovre, Denmark. nv@rheoscience.com
Phifer
Curtis B
CB
Corkern
Michele M
MM
Berthoud
Hans-Rudolf
HR
D000818:Animals; D001069:Appetite Regulation / Q000502:physiology; D013271:Gastric Dilatation / Q000378:metabolism* / Q000503:physiopathology; D005786:Gene Expression Regulation; D005934:Glucagon / Q000032:analysis*; D052216:Glucagon-Like Peptide 1; D008297:Male; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis*; D010455:Peptides / Q000032:analysis*; D011498:Protein Precursors / Q000032:analysis*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017552:Solitary Nucleus / Q000166:cytology / Q000378:metabolism*
D010446:Peptide Fragments; D010455:Peptides; D011498:Protein Precursors; D016760:Proto-Oncogene Proteins c-fos; D052216:Glucagon-Like Peptide 1; D005934:Glucagon