title: Knockdown of GLP-1 Receptors in Vagal Afferents Affects Normal Food Intake and Glycemia.
abstract: Nutrient stimulation of enteroendocrine L cells induces the release of the incretin and satiating peptide glucagon-like peptide 1 (GLP-1). The vagus nerve innervates visceral organs and may contribute to the mediation of gut-derived GLP-1's effects on food intake, energy homeostasis, and glycemic control. To test the hypothesis that vagal afferent neuron (VAN) GLP-1 receptors (GLP-1Rs) are necessary for these effects of endogenous GLP-1, we established a novel bilateral nodose ganglia injection technique to deliver a lentiviral vector and to knock down VAN GLP-1Rs in male Sprague Dawley rats. We found that a full expression of VAN GLP-1Rs is not necessary for the maintenance of long-term energy balance in normal eating conditions. VAN GLP-1R knockdown (kd) did, however, increase meal size and accelerated gastric emptying. Moreover, postmeal glycemia was elevated and insulin release was blunted in GLP-1R kd rats, suggesting that VAN GLP-1Rs are physiological contributors to the neuroincretin effect after a meal. Collectively, our results highlight a crucial role for the VANs in mediating the effects of endogenous GLP-1 on food intake and glycemia and may promote the further development of GLP-1-based therapies.
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Zurich, Switzerland jean-philippe-krieger@ethz.ch.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Krieger
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Zurich, Switzerland.
authors.forename: Myrtha
authors.initials: M
authors.lastname: Arnold
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Zurich, Switzerland.
authors.forename: Klaus G
authors.initials: KG
authors.lastname: Pettersen
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Zurich, Switzerland.
authors.forename: Pius
authors.initials: P
authors.lastname: Lossel
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Zurich, Switzerland.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Langhans
authors.affiliation: Physiology and Behavior Laboratory, Institute of Food, Nutrition, and Health, ETH Zurich, Zurich, Switzerland.
authors.forename: Shin J
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D004435:Eating / Q000235:genetics*; D004734:Energy Metabolism / Q000235:genetics*; D005746:Gastric Emptying / Q000235:genetics; D055785:Gene Knockdown Techniques; D000067757:Glucagon-Like Peptide-1 Receptor / Q000235:genetics*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007422:Intestines / Q000294:innervation; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism*; D009620:Nodose Ganglion / Q000378:metabolism*; D019518:Postprandial Period; D051381:Rats; D017207:Rats, Sprague-Dawley; D014630:Vagus Nerve / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin