2014 Jun 20:en20132092. [Epub ahead of print]
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) thermogeneses. In a first series of experiments, whole body and BAT thermogeneses 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 (Δ9-THC) or the CB1 antagonist AM251. Whole body thermogenesis was measured by indirect calorimetry and BAT thermogenesis assessed from interscapular BAT (iBAT) temperature. Δ9-THC blunted the effects of MTII on energy expenditure and iBAT temperature, whereas AM251 tended to potentiate the MTII effects. Δ9-THC also blocked the stimulating effect of MTII on 14C-bromopalmitate and3H-deoxyglucose uptakes in iBAT. Additionally, Δ9-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 Δ9-THC or AM251 in the fourth ventricle of the brain. We demonstrated the ability of Δ9-THC to blunt MTII-induced iBAT temperature elevation. Δ9-THC also blocked the PVH effect of MTII on 14C-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.
- PMID:
24949658
[PubMed – as supplied by publisher]
