Monge-Roffarello Boris, Labbe Sebastien M, Roy Marie-Claude, Lemay Marie-Laurence, Coneggo Estelle, Samson Pierre, Lanfray Damien, Richard Denis
Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, Canada G1V 4G5.
Endocrinology. 2014 Sep;155(9):3448-58. doi: 10.1210/en.2013-2092. Epub 2014 Jun 20.
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.
本研究旨在探究大麻素受体1（CB1）在黑皮质素-4受体（MC4R）激动剂对全身及棕色脂肪组织（BAT）产热的刺激作用中的参与情况。在第一组实验中，向大鼠脑第三脑室注射MC4R激动剂黑素皮质素II（MTII）以及CB1激动剂δ9-四氢大麻酚（δ(9)-THC）或CB1拮抗剂AM251，以此研究全身及BAT产热情况。通过间接测热法测量全身产热，并根据肩胛间BAT（iBAT）温度评估BAT产热。δ(9)-THC减弱了MTII对能量消耗和iBAT温度的影响，而AM251则倾向于增强MTII的作用。δ(9)-THC还阻断了MTII对iBAT中(14)C-溴棕榈酸酯和(3)H-脱氧葡萄糖摄取的刺激作用。此外，δ(9)-THC减弱了MTII对过氧化物酶体增殖物激活受体γ共激活因子1-α（Pgc1α）、II型碘甲腺原氨酸脱碘酶（Dio2）、肉碱棕榈酰转移酶1B（Cpt1b）和解偶联蛋白1（Ucp1）表达的刺激作用。在第二组实验中，我们探讨了下丘脑室旁核（PVH）在MTII对iBAT产热的CB1介导效应中的参与情况，通过向脑第四脑室注射MTII以及δ(9)-THC或AM251来评估iBAT产热。我们证实了δ(9)-THC能够减弱MTII诱导的iBAT温度升高。δ(9)-THC还阻断了MTII对iBAT中(14)C-溴棕榈酸酯摄取以及Pgc1α和Dio2表达的PVH效应。总之，本研究结果表明PVH参与了MC4R激动剂MTII对全身及BAT产热的CB1介导刺激作用。
