TY - JOUR
T1 - Cannabinoid receptor 1 in the Vagus nerve is dispensable for body weight homeostasis but required for normal gastrointestinal motility
AU - Vianna, Claudia R.
AU - Donato, Jose
AU - Rossi, Jari
AU - Scott, Michael
AU - Economides, Kyriakos
AU - Gautron, Lauren
AU - Pierpont, Stephanie
AU - Elias, Carol F.
AU - Elmquist, Joel K.
PY - 2012/7/25
Y1 - 2012/7/25
N2 - The cannabinoid receptor 1 (CB1R) is required for body weight homeostasis and normal gastrointestinal motility. However, the specific cell types expressing CB1Rthat regulate these physiological functions are unknown. CB1Ris 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 CB1R in neurons of the vagus nerve on metabolic homeostasis and gastrointestinal motility, we generated and characterized mice lacking CB1R in afferent and efferent branches of the vagus nerve (Cnr1flox/flox; Phox2b-Cre mice). On a chow or on a high-fat diet, Cnr1flox/flox; Phox2b-Cre mice have similar body weight, food intake, energy expenditure, and glycemia compared with Cnr1flox/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] (CB1R inverse agonist) paradigms, mutants display normal body weight and food intake. Interestingly, Cnr1flox/flox; Phox2b-Cre mice have increased gastrointestinal motility compared with controls. These results unveil CB1R in the vagus nerve as a key component underlying normal gastrointestinal motility.
AB - The cannabinoid receptor 1 (CB1R) is required for body weight homeostasis and normal gastrointestinal motility. However, the specific cell types expressing CB1Rthat regulate these physiological functions are unknown. CB1Ris 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 CB1R in neurons of the vagus nerve on metabolic homeostasis and gastrointestinal motility, we generated and characterized mice lacking CB1R in afferent and efferent branches of the vagus nerve (Cnr1flox/flox; Phox2b-Cre mice). On a chow or on a high-fat diet, Cnr1flox/flox; Phox2b-Cre mice have similar body weight, food intake, energy expenditure, and glycemia compared with Cnr1flox/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] (CB1R inverse agonist) paradigms, mutants display normal body weight and food intake. Interestingly, Cnr1flox/flox; Phox2b-Cre mice have increased gastrointestinal motility compared with controls. These results unveil CB1R in the vagus nerve as a key component underlying normal gastrointestinal motility.
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U2 - 10.1523/JNEUROSCI.4507-11.2012
DO - 10.1523/JNEUROSCI.4507-11.2012
M3 - Article
C2 - 22836266
AN - SCOPUS:84864267839
SN - 0270-6474
VL - 32
SP - 1031
EP - 1037
JO - Journal of Neuroscience
JF - Journal of Neuroscience
IS - 30
ER -