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大麻二酚对H9c2心肌细胞进行短期孵育可减轻脂质过载条件下二酰甘油的积累。

Short-Term Incubation of H9c2 Cardiomyocytes with Cannabigerol Attenuates Diacylglycerol Accumulation in Lipid Overload Conditions.

作者信息

Dziemitko Sylwia, Chabowski Adrian, Harasim-Symbor Ewa

机构信息

Department of Physiology, Medical University of Bialystok, Mickiewicz Str. 2C, 15-222 Bialystok, Poland.

出版信息

Cells. 2025 Jun 30;14(13):998. doi: 10.3390/cells14130998.

Abstract

Fatty acids (FAs) play a crucial role in human physiology, including energy production and serving as signaling molecules. However, a dysregulation in their balance can lead to multiple disorders, such as obesity and metabolic syndrome. These pathological conditions alter the balance between the heart's energetic substrates, promoting an increased reliance on FAs and decreased cardiac efficiency. A therapeutic application of a non-psychotropic phytocannabinoid, cannabigerol (CBG), seems to be a promising target since it interacts with different receptors and ion channels, including cannabinoid receptors-CB and CB, α2 adrenoceptor, or 5-hydroxytryptamine receptor. Therefore, in the current study, we evaluated a concentration-dependent effect of CBG (2.5 µM, 5 µM, and 10 µM) on H9c2 cardiomyocytes in lipid overload conditions. Gas-liquid chromatography and Western blotting techniques were used to determine the cellular lipid content and the level of selected proteins involved in FA metabolism, glucose transport, and the insulin signaling pathway. The glucose uptake assay was performed using a colorimetric method. Eighteen-hour CBG treatment in the highest concentration (10 µM) significantly diminished the accumulation of diacylglycerols (DAGs) and the saturation status of this lipid fraction. Moreover, the same concentration of CBG markedly decreased the level of FA transporters, namely fatty acid translocase (CD36) and plasma membrane fatty acid-binding protein (FABPpm), in the presence of palmitate (PA) in the culture medium. The results of our experiment suggest that CBG can significantly modulate lipid storage and composition in cardiomyocytes, thereby protecting against lipid-induced cellular dysfunction.

摘要

脂肪酸(FAs)在人体生理过程中发挥着关键作用,包括能量产生以及作为信号分子。然而,其平衡失调会导致多种疾病,如肥胖症和代谢综合征。这些病理状况会改变心脏能量底物之间的平衡,促使对脂肪酸的依赖增加,心脏效率降低。一种非精神活性植物大麻素——大麻二酚(CBG)的治疗应用似乎是一个有前景的靶点,因为它能与不同的受体和离子通道相互作用,包括大麻素受体-CB1和CB2、α2肾上腺素能受体或5-羟色胺受体。因此,在本研究中,我们评估了CBG(2.5 μM、5 μM和10 μM)在脂质过载条件下对H9c2心肌细胞的浓度依赖性影响。采用气液色谱法和蛋白质印迹技术来测定细胞脂质含量以及参与脂肪酸代谢、葡萄糖转运和胰岛素信号通路的特定蛋白质水平。葡萄糖摄取试验采用比色法进行。用最高浓度(10 μM)的CBG处理18小时可显著减少二酰基甘油(DAGs)的积累以及该脂质组分的饱和状态。此外,在培养基中存在棕榈酸(PA)的情况下,相同浓度的CBG显著降低了脂肪酸转运蛋白的水平,即脂肪酸转位酶(CD36)和质膜脂肪酸结合蛋白(FABPpm)。我们的实验结果表明,CBG可显著调节心肌细胞中的脂质储存和组成,从而防止脂质诱导的细胞功能障碍。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8071/12249120/a605fbb0f9d6/cells-14-00998-g001.jpg

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