A Mitochondrial-Targeted Coenzyme Q Analog Prevents Weight Gain and Ameliorates Hepatic Dysfunction in High-Fat-Fed Mice
A Mitochondrial-Targeted Coenzyme Q Analog Prevents Weight Gain and Ameliorates Hepatic Dysfunction in High-Fat-Fed Mice
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DOI：
10.1124/jpet.114.219329
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发表时间：
2014-12-01
影响因子：
3.5
通讯作者：
Sivitz, William I.
中科院分区：
文献类型：
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作者：
Fink, Brian D.;Herlein, Judith A.;Sivitz, William I.
我们假设线粒体靶向抗氧化剂，线粒体醌（mitoQ），已知具有线粒体解偶联特性，可能通过增加能量消耗而不是减少能量摄入来预防肥胖的发展和减轻肝功能障碍。我们给喂食高脂肪（HF）或正常脂肪（NF）饮食的肥胖易感C57BL/6小鼠注射mitoQ或乙醇。饮水中加入MitoQ （500 μ M）或载体（乙醇）28周。MitoQ显著降低了hf喂养小鼠的总体重和脂肪量，但对NF小鼠的这些参数没有影响。在喂食高热量食物的小鼠中，mitoQ减少了食物摄入量，而喂食低热量食物的小鼠则没有。在NF-和hf喂养的小鼠中，mitoQ减少了平均每日饮水量。下丘脑神经肽Y、针刺相关肽和瘦素受体长型的表达在HF小鼠中减少，而在NF小鼠中没有减少。肝脏总脂肪和甘油三酯含量在mitoq处理和对照组hf喂养的小鼠之间没有差异。然而，mitoQ显著降低肝脏脂质氢过氧化物和降低循环丙氨酸转氨酶，这是肝功能的标志。MitoQ不改变全身氧消耗或肝脏线粒体氧利用、膜电位、ATP产生或活性氧的产生。总之，在饮用水中添加mitoQ可以减轻肥胖的发展。与我们的假设相反，这种机制可能涉及下丘脑水平介导的能量摄入减少。MitoQ还通过其抗氧化特性改善hf诱导的肝功能障碍，而不改变肝脏脂肪或线粒体生物能量。
We hypothesized that the mitochondrial-targeted antioxidant, mitoquinone (mitoQ), known to have mitochondrial uncoupling properties, might prevent the development of obesity and mitigate liver dysfunction by increasing energy expenditure, as opposed to reducing energy intake. We administered mitoQ or vehicle (ethanol) to obesity-prone C57BL/6 mice fed high-fat (HF) or normal-fat (NF) diets. MitoQ (500 mu M) or vehicle (ethanol) was added to the drinking water for 28 weeks. MitoQ significantly reduced total body mass and fat mass in the HF-fed mice but had no effect on these parameters in NF mice. Food intake was reduced by mitoQ in the HF-fed but not in the NF-fed mice. Average daily water intake was reduced by mitoQ in both the NF- and HF-fed mice. Hypothalamic expression of neuropeptide Y, agouti-related peptide, and the long form of the leptin receptor were reduced in the HF but not in the NF mice. Hepatic total fat and triglyceride content did not differ between the mitoQ-treated and control HF-fed mice. However, mitoQ markedly reduced hepatic lipid hydroperoxides and reduced circulating alanine aminotransferase, a marker of liver function. MitoQ did not alter whole-body oxygen consumption or liver mitochondrial oxygen utilization, membrane potential, ATP production, or production of reactive oxygen species. In summary, mitoQ added to drinking water mitigated the development of obesity. Contrary to our hypothesis, the mechanism involved decreased energy intake likely mediated at the hypothalamic level. MitoQ also ameliorated HF-induced liver dysfunction by virtue of its antioxidant properties without altering liver fat or mitochondrial bioenergetics.