科研之友
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摘要
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 delta 9-tetrahydrocannabinol (delta(9)-THC) or the CB1 antagonist AM251. Whole-body thermogenesis was measured by indirect calorimetry and BAT thermogenesis assessed from interscapular BAT (iBAT) temperature. delta(9)-THC blunted the effects of MTII on energy expenditure and iBAT temperature, whereas AM251 tended to potentiate the MTII effects. delta(9)-THC also blocked the stimulating effect of MTII on C-14-bromopalmitate and H-3-deoxyglucose uptakes in iBAT. Additionally, delta(9)-THC attenuated the stimulating effect of MTII on the expression of peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (Pgc1 alpha), 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 delta(9)-THC or AM251 in the fourth ventricle of the brain. We demonstrated the ability of delta(9)-THC to blunt MTII-induced iBAT temperature elevation. delta(9)-THC also blocked the PVH effect of MTII on C-14-bromopalmitate uptake as well as on Pgc1 alpha 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.
- 出版日期2014-9
