Krott Lucia M, Piscitelli Fabiana, Heine Markus, Borrino Simona, Scheja Ludger, Silvestri Cristoforo, Heeren Joerg, Di Marzo Vincenzo
Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg Eppendorf, 20246 Hamburg, Germany.
Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, 80078 Pozzuoli, Naples, Italy.
J Lipid Res. 2016 Mar;57(3):464-73. doi: 10.1194/jlr.M065227. Epub 2016 Jan 14.
The endocannabinoids and their main receptor, cannabinoid type-1 (CB1), suppress intracellular cyclic AMP levels and have emerged as key players in the control of energy metabolism. CB1 agonists and blockers have been reported to influence the thermogenic function of white and brown adipose tissue (WAT and BAT), affecting body weight through the inhibition and stimulation of energy expenditure, respectively. The purpose of the current study was to investigate the regulation of the endocannabinoid system in WAT and BAT following exposure to either cold or specific agonism of β3-adrenoceptors using CL316,243 (CL), conditions known to cause BAT activation and WAT browning. To address this question, we performed quantitative PCR-based mRNA profiling of genes important for endocannabinoid synthesis, degradation, and signaling, and determined endocannabinoid levels by LC-MS in WAT and BAT of control, cold-exposed, and CL-treated wild-type mice as well as primary brown adipocytes. Treatment with CL and exposure to cold caused an upregulation of endocannabinoid levels and biosynthetic enzymes in WAT. Acute β3-adrenoceptor activation increased endocannabinoids and a subset of genes of biosynthesis in BAT and primary brown adipocytes. We suggest that the cold-mediated increase in endocannabinoid tone is part of autocrine negative feed-back mechanisms controlling β3-adrenoceptor-induced BAT activation and WAT browning.
内源性大麻素及其主要受体——大麻素1型（CB1）受体，可抑制细胞内环磷酸腺苷（cAMP）水平，并且已成为能量代谢调控中的关键因子。据报道，CB1激动剂和阻滞剂分别通过抑制和刺激能量消耗来影响白色和棕色脂肪组织（WAT和BAT）的产热功能，进而影响体重。本研究的目的是探究在暴露于寒冷环境或使用CL316,243（CL）特异性激动β3肾上腺素能受体后，白色和棕色脂肪组织中内源性大麻素系统的调节情况，已知这些条件会导致棕色脂肪组织激活和白色脂肪组织褐色化。为解决这个问题，我们对参与内源性大麻素合成、降解和信号传导的重要基因进行了基于定量PCR的mRNA分析，并通过液相色谱-质谱联用（LC-MS）测定了对照小鼠、冷暴露小鼠以及CL处理的野生型小鼠的白色和棕色脂肪组织以及原代棕色脂肪细胞中的内源性大麻素水平。CL处理和冷暴露导致白色脂肪组织中内源性大麻素水平和生物合成酶上调。急性β3肾上腺素能受体激活增加了棕色脂肪组织和原代棕色脂肪细胞中的内源性大麻素以及一部分生物合成基因。我们认为，寒冷介导的内源性大麻素水平升高是控制β3肾上腺素能受体诱导的棕色脂肪组织激活和白色脂肪组织褐色化的自分泌负反馈机制的一部分。
