title: The PVH as a site of CB1-mediated stimulation of thermogenesis by MC4R agonism in male rats.
abstract: The present study was designed to investigate the involvement of the cannabinoid receptor 1 (CB1) in the stimulating effects of the melanocortin-4 receptor (MC4R) agonism on whole-body and brown adipose tissue (BAT) thermogenesis. In a first series of experiments, whole-body and BAT thermogenesis were investigated in rats infused in the third ventricle of the brain with the MC4R agonist melanotan II (MTII) and the CB1 agonist δ9-tetrahydrocannabinol (δ(9)-THC) or the CB1 antagonist AM251. Whole-body thermogenesis was measured by indirect calorimetry and BAT thermogenesis assessed from interscapular BAT (iBAT) temperature. δ(9)-THC blunted the effects of MTII on energy expenditure and iBAT temperature, whereas AM251 tended to potentiate the MTII effects. δ(9)-THC also blocked the stimulating effect of MTII on (14)C-bromopalmitate and (3)H-deoxyglucose uptakes in iBAT. Additionally, δ(9)-THC attenuated the stimulating effect of MTII on the expression of peroxisome proliferator-activated receptor-γ coactivator 1-α (Pgc1α), type II iodothyronine deiodinase (Dio2), carnitine palmitoyltransferase 1B (Cpt1b), and uncoupling protein 1 (Ucp1). In a second series of experiments, we addressed the involvement of the paraventricular hypothalamic nucleus (PVH) in the CB1-mediated effects of MTII on iBAT thermogenesis, which were assessed following the infusion of MTII in the PVH and δ(9)-THC or AM251 in the fourth ventricle of the brain. We demonstrated the ability of δ(9)-THC to blunt MTII-induced iBAT temperature elevation. δ(9)-THC also blocked the PVH effect of MTII on (14)C-bromopalmitate uptake as well as on Pgc1α and Dio2 expression in iBAT. Altogether the results of this study demonstrate the involvement of the PVH in the CB1-mediated stimulating effects of the MC4R agonist MTII on whole-body and BAT thermogenesis.
authors.affiliation: Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada G1V 4G5.
authors.forename: Boris
authors.initials: B
authors.lastname: Monge-Roffarello
authors.forename: Sebastien M
authors.initials: SM
authors.lastname: Labbe
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Roy
authors.forename: Marie-Laurence
authors.initials: ML
authors.lastname: Lemay
authors.forename: Estelle
authors.initials: E
authors.lastname: Coneggo
authors.forename: Pierre
authors.initials: P
authors.lastname: Samson
authors.forename: Damien
authors.initials: D
authors.lastname: Lanfray
authors.forename: Denis
authors.initials: D
authors.lastname: Richard
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D008297:Male; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism*; D010456:Peptides, Cyclic / Q000378:metabolism*; D010880:Piperidines; D011720:Pyrazoles; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D044105:Receptor, Melanocortin, Type 4 / Q000819:agonists* / Q000378:metabolism; D022722:Thermogenesis; D000521:alpha-MSH / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: C543264:Cnr1 protein, rat; D010456:Peptides, Cyclic; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D044105:Receptor, Melanocortin, Type 4; C079282:melanotan-II; C103505:AM 251; D000521:alpha-MSH