Laboratory of Molecular Nutrition, Huazhong Agricultural University, Wuhan 430070, China.
Diabetes and Nutritional Sciences Division, School of Medicine, King's College London, London, UK.
Food Chem. 2021 Oct 30;360:129814. doi: 10.1016/j.foodchem.2021.129814. Epub 2021 May 12.
At present, the harmful effects and relevant mechanism of oxidized fish oils on fish and fish cells remain unknown. Our study found that oxidized fish oils increased lipogenesis, and reduced lipolysis, activated oxidative stress by decreasing glutathione peroxidase (GPX) activity, increasing malondialdhyde (MDA) content and damaging mitochondrial structure, and activated autophagy in the liver of yellow catfish; oxidized eicosapentaenoic acid (oxEPA) induced oxidative stress in yellow catfish hepatocytes. Oxidative stress, mitochondrial dysfunction and lipophagy mediated oxEPA induced-variations in lipid metabolism. Our further investigation indicated that oxEPA-activated lipophagy was via inhibiting the DNA binding capacity of the cAMP-response element binding protein (CREB)-1 to the region of Bcl-2 promoter, which in turn suppressed the binding activity of Bcl-2 to Beclin1 and promoted autophagosome formation. For the first time, our study elucidated the mechanisms of oxidized fish oils-induced lipid deposition by the oxidative stress, mitochondrial dysfunction and CREB1-Bcl-2-Beclin1 pathway in fish.
目前，氧化鱼油对鱼类和鱼类细胞的有害影响及其相关机制尚不清楚。我们的研究发现，氧化鱼油通过增加脂肪生成、减少脂肪分解、降低谷胱甘肽过氧化物酶 (GPX) 活性、增加丙二醛 (MDA) 含量和损伤线粒体结构来激活黄颡鱼肝的氧化应激，同时激活自噬；氧化二十碳五烯酸 (oxEPA) 在黄颡鱼肝细胞中诱导氧化应激。氧化应激、线粒体功能障碍和脂自噬介导了 oxEPA 诱导的脂质代谢变化。我们的进一步研究表明，oxEPA 激活的脂自噬是通过抑制 cAMP 反应元件结合蛋白 (CREB)-1 与 Bcl-2 启动子区域的 DNA 结合能力，从而抑制 Bcl-2 与 Beclin1 的结合活性并促进自噬体形成。本研究首次阐明了氧化应激、线粒体功能障碍和 CREB1-Bcl-2-Beclin1 通路在鱼类中氧化鱼油诱导脂质沉积的机制。
