米托醌对肥胖和糖尿病大鼠肝脏代谢和脂肪变性的影响

Effect of mitoquinone on liver metabolism and steatosis in obese and diabetic rats

Keywords：Antioxidants, Glucose, Insulin, Liver, Mitochondria, Obesity, Oxidative stress, Steatosis 

关键词：抗氧化剂、葡萄糖、胰岛素、肝脏、线粒体、肥胖、氧化应激、脂肪变性 
作者：Fink Brian D , Yu Liping , Coppey Lawrence , Obrosov Alexander , Shevalye Hanna , Kerns Robert J , Yorek Mark A , Sivitz William I
出版期刊：《Pharmacol Res Perspect》（2021）

Abstract：

Previous work by ourselves and others showed that mitoquinone (mitoQ) reduced oxidative damage and prevented hepatic fat accumulation in mice made obese with high-fat (HF) feeding. Here we extended these studies to examine the effect of mitoQ on parameters affecting liver function in rats treated with HF to induce obesity and in rats treated with HF plus streptozotocin (STZ) to model a severe form of type 2 diabetes. In prior reported work, we found that mitoQ significantly improved glycemia based on glucose tolerance data in HF rats but not in the diabetic rats. Here we found only non-significant reductions in insulin and glucose measured in the fed state at sacrifice in the HF mice treated with mitoQ. Metabolomic data showed that mitoQ altered several hepatic metabolic pathways in HF-fed obese rats toward those observed in control normal chow-fed non-obese rats. However, mitoQ had little effect on pathways observed in the diabetic rats, wherein diabetes itself induced marked pathway aberrations. MitoQ did not alter respiration or membrane potential in isolated liver mitochondria. MitoQ reduced liver fat and liver hydroperoxide levels but did not improve liver function as marked by circulating levels of aspartate and alanine aminotransferase (ALT). In summary, our results for HF-fed rats are consistent with past findings in HF-fed mice indicating decreased liver lipid hydroperoxides (LPO) and improved glycemia. However, in contrast to the HF obese mice, mitoQ did not improve glycemia or reset perturbed metabolic pathways in the diabetic rats.

文章摘要：

我们和其他人之前的工作表明，在高脂 (HF) 喂养的肥胖小鼠中，米托醌 (mitoQ) 可减少氧化损伤并防止肝脏脂肪堆积。在这里，我们扩展了这些研究，以检查 mitoQ 对用 HF 治疗以诱导肥胖的大鼠和用 HF 加链脲佐菌素 (STZ) 治疗以模拟严重形式的 2 型糖尿病的大鼠肝功能参数的影响。在先前报道的工作中，我们发现基于 HF 大鼠的葡萄糖耐量数据，mitoQ 显着改善了血糖，但在糖尿病大鼠中没有。在这里，我们发现在用 mitoQ 治疗的 HF 小鼠中，在进食状态下测量的胰岛素和葡萄糖仅没有显着降低。代谢组学数据显示，mitoQ 将 HF 喂养的肥胖大鼠的几种肝脏代谢途径改变为在对照正常食物喂养的非肥胖大鼠中观察到的那些。然而，mitoQ 对在糖尿病大鼠中观察到的通路几乎没有影响，其中糖尿病本身会引起显着的通路异常。 MitoQ 没有改变离体肝线粒体的呼吸或膜电位。 MitoQ 降低了肝脏脂肪和肝脏氢过氧化物水平，但没有改善肝功能，这以天冬氨酸和丙氨酸氨基转移酶 (ALT) 的循环水平为标志。总之，我们对 HF 喂养大鼠的结果与过去在 HF 喂养小鼠中的发现一致，表明肝脏脂质氢过氧化物 (LPO) 降低和血糖改善。然而，与 HF 肥胖小鼠相比，mitoQ 并未改善糖尿病大鼠的血糖或重置扰乱的代谢途径。

点击链接即可查看和下载文章：https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866483/pdf/PRP2-9-e00701.pdf

文章题目、关键词与摘要译文仅用于参考。