title: Cannabinoid receptor 1 in the vagus nerve is dispensable for body weight homeostasis but required for normal gastrointestinal motility.
abstract: The cannabinoid receptor 1 (CB(1)R) is required for body weight homeostasis and normal gastrointestinal motility. However, the specific cell types expressing CB(1)R that regulate these physiological functions are unknown. CB(1)R is widely expressed, including in neurons of the parasympathetic branches of the autonomic nervous system. The vagus nerve has been implicated in the regulation of several aspects of metabolism and energy balance (e.g., food intake and glucose balance), and gastrointestinal functions including motility. To directly test the relevance of CB(1)R in neurons of the vagus nerve on metabolic homeostasis and gastrointestinal motility, we generated and characterized mice lacking CB(1)R in afferent and efferent branches of the vagus nerve (Cnr1(flox/flox); Phox2b-Cre mice). On a chow or on a high-fat diet, Cnr1(flox/flox); Phox2b-Cre mice have similar body weight, food intake, energy expenditure, and glycemia compared with Cnr1(flox/flox) control mice. Also, fasting-induced hyperphagia and after acute or chronic pharmacological treatment with SR141716 [N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole carboxamide] (CB(1)R inverse agonist) paradigms, mutants display normal body weight and food intake. Interestingly, Cnr1(flox/flox); Phox2b-Cre mice have increased gastrointestinal motility compared with controls. These results unveil CB(1)R in the vagus nerve as a key component underlying normal gastrointestinal motility.
authors: Department of Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9077, USA. claudia.vianna@utsouthwestern.edu
authors: Claudia R
authors: CR
authors: Vianna
authors: Jose
authors: J
authors: Donato
authors: Jari
authors: J
authors: Rossi
authors: Michael
authors: M
authors: Scott
authors: Kyriakos
authors: K
authors: Economides
authors: Lauren
authors: L
authors: Gautron
authors: Stephanie
authors: S
authors: Pierpont
authors: Carol F
authors: CF
authors: Elias
authors: Joel K
authors: JK
authors: Elmquist
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000235:genetics*; D059305:Diet, High-Fat; D004435:Eating / Q000187:drug effects / Q000235:genetics; D005508:Food Deprivation; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000235:genetics*; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics*; D006963:Hyperphagia / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000077285:Rimonabant; D014630:Vagus Nerve / Q000378:metabolism*
chemical_list: C543264:Cnr1 protein, rat; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant