INSERM U1215 Neurocentre Magendie, Université de Bordeaux, 33077 Bordeaux, France.
Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, 60121 Ancona, Italy.
Cells. 2022 Aug 19;11(16):2582. doi: 10.3390/cells11162582.
Via activation of the cannabinoid type-1 (CB) receptor, endogenous and exogenous cannabinoids modulate important biochemical and cellular processes in adipocytes. Several pieces of evidence suggest that alterations of mitochondrial physiology might be a possible mechanism underlying cannabinoids' effects on adipocyte biology. Many reports suggest the presence of CB receptor mRNA in both white and brown adipose tissue, but the detailed subcellular localization of CB protein in adipose cells has so far been scarcely addressed. In this study, we show the presence of the functional CB receptor at different subcellular locations of adipocytes from epididymal white adipose tissue (eWAT) depots. We observed that CB is located at different subcellular levels, including the plasma membrane and in close association with mitochondria (mtCB). Functional analysis in tissue homogenates and isolated mitochondria allowed us to reveal that cannabinoids negatively regulate complex-I-dependent oxygen consumption in eWAT. This effect requires mtCB activation and consequent regulation of the intramitochondrial cAMP-PKA pathway. Thus, CB receptors are functionally present at the mitochondrial level in eWAT adipocytes, adding another possible mechanism for peripheral regulation of energy metabolism.
通过激活大麻素类型 1（CB）受体，内源性和外源性大麻素可以调节脂肪细胞中的重要生化和细胞过程。有几项证据表明，线粒体生理学的改变可能是大麻素对脂肪细胞生物学影响的潜在机制。许多报告表明，CB 受体 mRNA 存在于白色和棕色脂肪组织中，但迄今为止，脂肪细胞中 CB 蛋白的详细亚细胞定位尚未得到充分解决。在这项研究中，我们显示了来自附睾白色脂肪组织（eWAT）库的脂肪细胞中不同亚细胞位置存在功能性 CB 受体。我们观察到 CB 位于不同的亚细胞水平，包括质膜和与线粒体（mtCB）密切相关。组织匀浆和分离线粒体中的功能分析使我们能够揭示大麻素可负调控 eWAT 中依赖于复合物-I 的耗氧量。这种效应需要 mtCB 的激活以及随后对线粒体腔内 cAMP-PKA 途径的调节。因此，CB 受体在 eWAT 脂肪细胞的线粒体水平上具有功能性，为外周能量代谢调节增加了另一种可能的机制。
