Departamento de Fisiología, Facultad de Medicina, Universidad Complutense de Madrid-Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain.
Institut de Recerca del Hospital de la Santa Creu i Sant Pau, Instituto de Investigaciones Biomédicas (IIB)-Sant Pau, Barcelona, Spain.
FASEB J. 2019 Nov;33(11):12060-12072. doi: 10.1096/fj.201900347RR. Epub 2019 Aug 1.
The impact of the mitochondria-targeted antioxidant MitoQ was evaluated in the metabolic alterations and the adipose tissue remodeling associated with obesity. Male Wistar rats were fed either a high-fat diet (HFD; 35% fat) or a standard diet (3.5% fat) for 7 wk and treated with MitoQ (200 µM). A proteomic analysis of visceral adipose tissue from patients with obesity and patients without obesity was performed. MitoQ partially prevented the increase in body weight, adiposity, homeostasis model assessment index, and adipose tissue remodeling in HFD rats. It also ameliorated protein level changes of factors involved in insulin signaling observed in adipose tissue of obese rats: reductions in adiponectin and glucose transporter 4 (GLUT 4) and increases in dipeptidylpeptidase 4, suppressor of cytokine signaling 3 (SOCS3), and insulin receptor substrate 1 phosphorylation. MitoQ prevented down-regulation of adiponectin and GLUT 4 and increases in SOCS3 levels in a TNF-α-induced insulin-resistant 3T3-L1 adipocyte model. MitoQ also ameliorated alterations in mitochondrial proteins observed in obese rats: increases in cyclophylin F and carnitine palmitoyl transferase 1A and reductions in mitofusin1, peroxiredoxin 4, and fumarate hydratase. The proteomic analysis of the visceral adipose tissue from patients with obesity show alterations in mitochondrial proteins similar to those observed in obese rats. Therefore, the data show the beneficial effect of MitoQ in the metabolic dysfunction induced by obesity.-Marín-Royo, G., Rodríguez, C., Le Pape, A., Jurado-López, R., Luaces, M., Antequera, A., Martínez-González, J., Souza-Neto, F. V., Nieto, M. L., Martínez-Martínez, E., Cachofeiro, V. The role of mitochondrial oxidative stress in the metabolic alterations in diet-induced obesity in rats.
线粒体靶向抗氧化剂 MitoQ 对肥胖相关代谢改变和脂肪组织重塑的影响进行了评估。雄性 Wistar 大鼠连续 7 周喂食高脂肪饮食（HFD；35%脂肪）或标准饮食（3.5%脂肪），并接受 MitoQ（200μM）治疗。对肥胖患者和非肥胖患者的内脏脂肪组织进行了蛋白质组学分析。MitoQ 部分预防了 HFD 大鼠体重、肥胖、稳态模型评估指数和脂肪组织重塑的增加。它还改善了肥胖大鼠脂肪组织中涉及胰岛素信号的因子的蛋白质水平变化：脂联素和葡萄糖转运蛋白 4（GLUT4）减少，二肽基肽酶 4、细胞因子信号转导抑制物 3（SOCS3）和胰岛素受体底物 1 磷酸化增加。MitoQ 可防止 TNF-α诱导的胰岛素抵抗 3T3-L1 脂肪细胞模型中脂联素和 GLUT4 的下调以及 SOCS3 水平的升高。MitoQ 还改善了肥胖大鼠观察到的线粒体蛋白改变：细胞色素 P450 F 环蛋白和肉碱棕榈酰转移酶 1A 增加，而线粒体融合蛋白 1、过氧化物还原酶 4 和延胡索酸水合酶减少。肥胖患者内脏脂肪组织的蛋白质组学分析显示，线粒体蛋白发生了与肥胖大鼠观察到的类似改变。因此，数据显示 MitoQ 对肥胖引起的代谢功能障碍具有有益作用。
