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Aquaporin-9 is involved in the lipid-lowering activity of the nutraceutical silybin on hepatocytes through modulation of autophagy and lipid droplets composition.
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ( IF 3.9 ) Pub Date : 2019-12-06 , DOI: 10.1016/j.bbalip.2019.158586 Francesca Baldini 1 , Piero Portincasa 2 , Elena Grasselli 1 , Gianluca Damonte 3 , Annalisa Salis 1 , Michela Bonomo 4 , Marilina Florio 4 , Nadia Serale 1 , Adriana Voci 1 , Patrizia Gena 4 , Laura Vergani 1 , Giuseppe Calamita 4
Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids ( IF 3.9 ) Pub Date : 2019-12-06 , DOI: 10.1016/j.bbalip.2019.158586 Francesca Baldini 1 , Piero Portincasa 2 , Elena Grasselli 1 , Gianluca Damonte 3 , Annalisa Salis 1 , Michela Bonomo 4 , Marilina Florio 4 , Nadia Serale 1 , Adriana Voci 1 , Patrizia Gena 4 , Laura Vergani 1 , Giuseppe Calamita 4
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Hepatic steatosis is the hallmark of non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome and insulin resistance with potential evolution towards non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Key roles of autophagy and oxidative stress in hepatic lipid accumulation and NAFLD progression are recognized. Here, we employed a rat hepatoma cell model of NAFLD progression made of FaO cells exposed to oleate/palmitate followed or not by TNFα treatment to investigate the molecular mechanisms through which silybin, a lipid-lowering nutraceutical, may improve hepatic lipid dyshomeostasis. The beneficial effect of silybin was found to involve amelioration of the fatty acids profile of lipid droplets, stimulation of the mitochondrial oxidation and upregulation of a microRNA of pivotal relevance in hepatic fat metabolism, miR-122. Silybin was also found to restore the levels of Aquaporin-9 (AQP9) and glycerol permeability while reducing the activation of the oxidative stress-dependent transcription factor NF-κB, and autophagy turnover. In conclusion, silybin was shown to have molecular effects on signaling pathways that were previously unknown and potentially protect the hepatocyte. These actions intersect TG metabolism, fat-induced autophagy and AQP9-mediated glycerol transport in hepatocytes.
中文翻译：
Aquaporin-9通过调节自噬和脂质滴组成来参与营养保健水飞蓟宾对肝细胞的降脂活性。
肝脂肪变性是非酒精性脂肪肝疾病（NAFLD），代谢综合征的肝脏表现和胰岛素抵抗的标志，可能发展为非酒精性脂肪性肝炎（NASH），肝硬化和肝细胞癌。自噬和氧化应激在肝脂质蓄积和NAFLD进展中的关键作用已得到公认。在这里，我们采用了由暴露于油酸盐/棕榈酸盐的FaO细胞制成的NAFLD进展的大鼠肝癌细胞模型，然后进行TNFα处理，以研究水飞蓟宾（降脂营养品）可能改善肝脂质异常稳态的分子机制。发现水飞蓟宾的有益作用包括改善脂滴的脂肪酸分布，刺激线粒体氧化并上调肝脂肪代谢中至关重要的microRNA，miR-122。还发现了水飞蓟宾可以恢复水通道蛋白9（AQP9）和甘油的渗透性，同时减少氧化应激依赖性转录因子NF-κB的活化和自噬转换。总之，水飞蓟宾被证明对以前未知的信号通路具有分子作用，并可能保护肝细胞。这些作用与TG代谢，脂肪诱导的自噬和AQP9介导的甘油在肝细胞中的运输相交。总之，水飞蓟宾被证明对以前未知的信号通路具有分子作用，并可能保护肝细胞。这些作用与TG代谢，脂肪诱导的自噬和AQP9介导的甘油在肝细胞中的运输相交。总之，水飞蓟宾被证明对以前未知的信号通路具有分子作用，并可能保护肝细胞。这些作用与TG代谢，脂肪诱导的自噬和AQP9介导的甘油在肝细胞中的运输相交。
更新日期：2019-12-06
中文翻译：
Aquaporin-9通过调节自噬和脂质滴组成来参与营养保健水飞蓟宾对肝细胞的降脂活性。
肝脂肪变性是非酒精性脂肪肝疾病（NAFLD），代谢综合征的肝脏表现和胰岛素抵抗的标志，可能发展为非酒精性脂肪性肝炎（NASH），肝硬化和肝细胞癌。自噬和氧化应激在肝脂质蓄积和NAFLD进展中的关键作用已得到公认。在这里，我们采用了由暴露于油酸盐/棕榈酸盐的FaO细胞制成的NAFLD进展的大鼠肝癌细胞模型，然后进行TNFα处理，以研究水飞蓟宾（降脂营养品）可能改善肝脂质异常稳态的分子机制。发现水飞蓟宾的有益作用包括改善脂滴的脂肪酸分布，刺激线粒体氧化并上调肝脂肪代谢中至关重要的microRNA，miR-122。还发现了水飞蓟宾可以恢复水通道蛋白9（AQP9）和甘油的渗透性，同时减少氧化应激依赖性转录因子NF-κB的活化和自噬转换。总之，水飞蓟宾被证明对以前未知的信号通路具有分子作用，并可能保护肝细胞。这些作用与TG代谢，脂肪诱导的自噬和AQP9介导的甘油在肝细胞中的运输相交。总之，水飞蓟宾被证明对以前未知的信号通路具有分子作用，并可能保护肝细胞。这些作用与TG代谢，脂肪诱导的自噬和AQP9介导的甘油在肝细胞中的运输相交。总之，水飞蓟宾被证明对以前未知的信号通路具有分子作用，并可能保护肝细胞。这些作用与TG代谢，脂肪诱导的自噬和AQP9介导的甘油在肝细胞中的运输相交。
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