National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland.
International Institute of Translational Medicine, Jesionowa 11, 55-114 Malin, Poland.
Int J Mol Sci. 2023 Apr 12;24(8):7120. doi: 10.3390/ijms24087120.
The endoplasmic reticulum (ER) fulfills essential duties in cell physiology, and impairment of this organelle's functions is associated with a wide number of metabolic diseases. When ER stress is generated in the adipose tissue, it is observed that the metabolism and energy homeostasis of the adipocytes are altered, leading to obesity-associated metabolic disorders such as type 2 diabetes (T2D). In the present work, we aimed to evaluate the protective effects of Δ9-tetrahydrocannabivarin (THCV, a cannabinoid compound isolated from L.) against ER stress in adipose-derived mesenchymal stem cells. Our results show that pre-treatment with THCV prevents the subcellular alteration of cell components such as nuclei, F-actin, or mitochondria distribution, and restores cell migration, cell proliferation and colony-forming capacity upon ER stress. In addition, THCV partially reverts the effects that ER stress induces regarding the activation of apoptosis and the altered anti- and pro-inflammatory cytokine profile. This indicates the protective characteristics of this cannabinoid compound in the adipose tissue. Most importantly, our data demonstrate that THCV decreases the expression of genes involved in the unfolded protein response (UPR) pathway, which were upregulated upon induction of ER stress. Altogether, our study shows that the cannabinoid THCV is a promising compound that counters the harmful effects triggered by ER stress in the adipose tissue. This work paves the way for the development of new therapeutic means based on THCV and its regenerative properties to create a favorable environment for the development of healthy mature adipocyte tissue and to reduce the incidence and clinical outcome of metabolic diseases such as diabetes.
内质网(ER)在细胞生理学中履行重要职责,而该细胞器功能的损伤与许多代谢疾病有关。当脂肪组织中产生内质网应激时,观察到脂肪细胞的代谢和能量稳态发生改变,导致与肥胖相关的代谢紊乱,如 2 型糖尿病(T2D)。在本工作中,我们旨在评估 Δ9-四氢大麻酚酸(THCV,一种从 大麻属中分离出来的大麻素化合物)对脂肪来源间充质干细胞内质网应激的保护作用。我们的结果表明,THCV 预处理可防止细胞成分的亚细胞改变,如细胞核、F-肌动蛋白或线粒体分布,并在 ER 应激时恢复细胞迁移、增殖和集落形成能力。此外,THCV 部分逆转了 ER 应激诱导的细胞凋亡激活和抗炎及促炎细胞因子谱改变的作用。这表明这种大麻素化合物在脂肪组织中具有保护特性。最重要的是,我们的数据表明,THCV 降低了参与未折叠蛋白反应(UPR)途径的基因的表达,这些基因在 ER 应激诱导时上调。总之,我们的研究表明,大麻素 THCV 是一种有前途的化合物,可对抗脂肪组织中内质网应激引发的有害作用。这项工作为开发基于 THCV 及其再生特性的新治疗方法奠定了基础,以创造有利于健康成熟脂肪细胞组织发育的环境,并降低糖尿病等代谢疾病的发病率和临床结局。