Effect of mitoquinone (Mito-Q) on neuropathic endpoints in an obese and type 2 diabetic rat model
Effect of mitoquinone (Mito-Q) on neuropathic endpoints in an obese and type 2 diabetic rat model
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DOI：
10.1080/10715762.2020.1754409
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发表时间：
2020-04-23
影响因子：
3.3
通讯作者：
Yorek, Mark
中科院分区：
文献类型：
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作者：
Fink, Brian;Coppey, Lawrence;Yorek, Mark
本研究旨在确定在饮食中添加米托醌 (Mito-Q) 是否能有效治疗饮食引起的肥胖（糖尿病前期）和 2 型糖尿病动物模型中的周围神经病变。与其他用于治疗周围神经病变的抗氧化应激化合物不同，Mito-Q 专门针对线粒体。尽管 Mito-Q 已被证明可以减少线粒体产生的氧化应激，但尚未研究 Mito-Q 对饮食引起的肥胖或 2 型糖尿病引起的周围神经病变的影响。饮食诱导的肥胖（高脂肪饮食后 12 周）或 2 型糖尿病大鼠（高脂肪饮食 12 周，高血糖发生后 4 周）通过 Mito-Q（0.93 g/kg 饮食）饮食治疗 12 周。随后，检查了葡萄糖利用、神经外膜小动脉对乙酰胆碱的血管反应性以及周围神经病变相关的终点。在肥胖和糖尿病大鼠的饮食中添加 Mito-Q 可改善运动和/或感觉神经传导速度、角膜和表皮内神经纤维密度、角膜敏感性和热伤害感受。令人惊讶的是，用 Mito-Q 治疗肥胖和糖尿病大鼠并没有改善葡萄糖利用或神经外膜小动脉对乙酰胆碱的血管反应性。这些研究表明，线粒体功能障碍会导致糖尿病前期和晚期 2 型糖尿病动物模型中的周围神经病变。然而，Mito-Q 治疗后周围神经病变的改善与葡萄糖利用或神经外膜小动脉对乙酰胆碱的血管反应性的改善无关。
This study sought to determine whether the addition of mitoquinone (Mito-Q) in the diet is an effective treatment for peripheral neuropathy in animal models of diet-induced obesity (pre-diabetes) and type 2 diabetes. Unlike other anti-oxidative stress compounds investigated as a treatment for peripheral neuropathy, Mito-Q specifically targets mitochondria. Although mito-Q has been shown to reduce oxidative stress generated by mitochondria there have been no studies performed of the effect of Mito-Q on peripheral neuropathy induced by diet-induced obesity or type 2 diabetes. Diet-induced obese (12 weeks after high fat diet) or type 2 diabetic rats (12 weeks of high fat diet and 4 weeks after the onset of hyperglycemia) were treated via the diet with Mito-Q (0.93 g/kg diet) for 12 weeks. Afterwards, glucose utilization, vascular reactivity of epineurial arterioles to acetylcholine and peripheral neuropathy related endpoints were examined. The addition of Mito-Q to the diets of obese and diabetic rats improved motor and/or sensory nerve conduction velocity, cornea and intraepidermal nerve fibre density, cornea sensitivity and thermal nociception. Surprisingly, treating obese and diabetic rats with Mito-Q did not improve glucose utilization or vascular reactivity by epineurial arterioles to acetylcholine. These studies imply that mitochondrial dysfunction contributes to peripheral neuropathy in animal models of pre-diabetes and late-stage type 2 diabetes. However, improvement in peripheral neuropathy following treatment with Mito-Q was not associated with improvement in glucose utilization or vascular reactivity of epineurial arterioles to acetylcholine.