Effect of mitoquinone on liver metabolism and steatosis in obese and diabetic rats.
Effect of mitoquinone on liver metabolism and steatosis in obese and diabetic rats.
复制标题
米托醌对肥胖和糖尿病大鼠肝脏代谢和脂肪变性的影响。
DOI：
10.1002/prp2.701
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发表时间：
2021-03
影响因子：
2.6
通讯作者：
Sivitz WI
中科院分区：
文献类型：
--
作者：
Fink BD;Yu L;Coppey L;Obrosov A;Shevalye H;Kerns RJ;Yorek MA;Sivitz WI
我们和其他人之前的研究表明，mitoquinone （mitoQ）可以减少高脂肪（HF）喂养导致肥胖的小鼠的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，在HF诱导肥胖的大鼠和HF加链脲佐菌素（STZ）模拟严重2型糖尿病的大鼠中，研究mitoQ对影响肝功能参数的影响。在之前报道的工作中，我们发现mitoQ根据糖耐量数据显著改善HF大鼠的血糖，但在糖尿病大鼠中没有。在这里，我们发现，在喂食状态下，接受mitoQ治疗的HF小鼠在牺牲时，胰岛素和葡萄糖的含量只有非显著的降低。代谢组学数据显示，与正常饲料喂养的非肥胖大鼠相比，mitoQ改变了HF喂养的肥胖大鼠的几种肝脏代谢途径。然而，mitoQ对糖尿病大鼠中观察到的通路几乎没有影响，其中糖尿病本身诱导了明显的通路畸变。MitoQ不改变离体肝脏线粒体的呼吸作用或膜电位。MitoQ降低了肝脏脂肪和肝脏过氧化氢水平，但没有改善肝功能，这是由循环中的天冬氨酸和丙氨酸转氨酶（ALT）水平所标志的。总之，我们在高频喂养大鼠身上的结果与过去在高频喂养小鼠身上的发现一致，表明肝脏脂质氢过氧化物（LPO）减少，血糖水平改善。然而，与HF肥胖小鼠相比，mitoQ并没有改善糖尿病大鼠的血糖或重置紊乱的代谢途径。采用米托醌（MQ）或载药治疗高脂喂养肥胖和高脂喂养链脲佐菌素（STZ）糖尿病大鼠。
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. High fat fed obese and high fat fed streptozotocin (STZ) diabetic rats were treated with mitoquinone (MQ) or vehicle.
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影响因子：
--
作者：
Lim, Sangbin;Rashid, Md Abdur;Kim, Sung Soo
通讯作者：
Kim, Sung Soo
影响因子：
5
作者：
Davidson, Eric P.;Coppey, Lawrence J.;Yorek, Mark A.
通讯作者：
Yorek, Mark A.
穿透性阳离子增强了线粒体中阴离子质子团的解耦活性。
影响因子：
3.7
作者：
Antonenko YN;Khailova LS;Knorre DA;Markova OV;Rokitskaya TI;Ilyasova TM;Severina II;Kotova EA;Karavaeva YE;Prikhodko AS;Severin FF;Skulachev VP
通讯作者：
Skulachev VP
影响因子：
3.3
作者：
Fink, Brian;Coppey, Lawrence;Yorek, Mark
通讯作者：
Yorek, Mark
DOI：
10.1124/jpet.114.219329
发表时间：
2014-12-01
影响因子：
3.5
作者：
Fink, Brian D.;Herlein, Judith A.;Sivitz, William I.
通讯作者：
Sivitz, William I.