Escola Paulista de Medicina, Departamento de Fisiologia, Universidade Federal de São Paulo, São Paulo 04023-062, SP, Brazil.
Dipartimento di Chimica e Biologia "A. Zambelli", Università degli Studi di Salerno, 84084 Fisciano, SA, Italy.
Int J Mol Sci. 2021 Sep 10;22(18):9812. doi: 10.3390/ijms22189812.
Mitochondrial impairments in dynamic behavior (fusion/fission balance) associated with mitochondrial dysfunction play a key role in cell lipotoxicity and lipid-induced metabolic diseases. The present work aimed to evaluate dose- and time-dependent effects of the monounsaturated fatty acid oleate on mitochondrial fusion/fission proteins in comparison with the saturated fatty acid palmitate in hepatic cells. To this end, HepG-2 cells were treated with 0, 10 μM, 50 μM, 100 μM, 250 μM or 500 μM of either oleate or palmitate for 8 or 24 h. Cell viability and lipid accumulation were evaluated to assess lipotoxicity. Mitochondrial markers of fusion (mitofusin 2, MFN2) and fission (dynamin-related protein 1, DRP1) processes were evaluated by Western blot analysis. After 8 h, the highest dose of oleate induced a decrease in DRP1 content without changes in MFN2 content in association with cell viability maintenance, whereas palmitate induced a decrease in cell viability associated with a decrease mainly in MFN2 content. After 24 h, oleate induced MFN2 increase, whereas palmitate induced DRP1 increase associated with a higher decrease in cell viability with high doses compared to oleate. This finding could be useful to understand the role of mitochondria in the protective effects of oleate as a bioactive compound.
与线粒体功能障碍相关的动态行为（融合/裂变平衡）的线粒体损伤在细胞脂肪毒性和脂质诱导的代谢疾病中起着关键作用。本研究旨在评估单不饱和脂肪酸油酸与饱和脂肪酸棕榈酸相比，在剂量和时间依赖性方面对肝细 胞中线粒体融合/裂变蛋白的影响。为此，将 HepG-2 细胞用 0、10 μM、50 μM、100 μM、250 μM 或 500 μM 的油酸或棕榈酸处理 8 或 24 h。通过评估细胞活力和脂质积累来评估脂肪毒性。通过 Western blot 分析评估线粒体融合（线粒体融合蛋白 2，MFN2）和裂变（与 DRP1 相关的动力学蛋白 1）过程的线粒体标志物。8 h 后，油酸的最高剂量诱导 DRP1 含量降低，而 MFN2 含量不变，同时保持细胞活力，而棕榈酸诱导细胞活力降低，主要与 MFN2 含量降低有关。24 h 后，油酸诱导 MFN2 增加，而棕榈酸诱导 DRP1 增加，与细胞活力下降有关，高剂量组与油酸相比下降更明显。这一发现有助于理解线粒体在油酸作为生物活性化合物的保护作用中的作用。
