Mimp/Mtch2, an Obesity Susceptibility Gene, Induces Alteration of Fatty Acid Metabolism in Transgenic Mice
Mimp/Mtch2, an Obesity Susceptibility Gene, Induces Alteration of Fatty Acid Metabolism in Transgenic Mice
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DOI：
10.1371/journal.pone.0157850
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发表时间：
2016-06-30
期刊：
影响因子：
3.7
通讯作者：
Tsarfaty, Ilan
中科院分区：
文献类型：
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作者：
Bar-Lev, Yamit;Moshitch-Moshkovitz, Sharon;Tsarfaty, Ilan
目的脂肪肝、肥胖和胰岛素抵抗等代谢功能障碍是当今世界最常见的疾病之一，其患病率还在不断上升。MIMP/Mtch2是一种线粒体载体蛋白同源物，定位于线粒体，诱导线粒体去极化。MIMP/Mtch2单核苷酸多态与人类肥胖有关，小鼠肌肉中MIMP/Mtch2基因的缺失可以预防肥胖。我们的目的是研究MIMP/Mtch2过表达对体内的影响。方法对过表达MIMP/Mtch2-GFP的转基因小鼠进行鉴定和监测脂肪蓄积、体重和血糖。结果Mimp/Mtch2-GFP转基因小鼠表达高水平的脂肪酸合成酶和β-氧化基因，并发育成脂肪肝和肾脏。此外，高脂饮食喂养的MIMP/Mtch2小鼠表现出高血糖水平。结论MIMP/Mtch2改变脂代谢，可能在肥胖的发生、发展中起一定作用。
ObjectiveMetabolic dysfunctions, such as fatty liver, obesity and insulin resistance, are among the most common contemporary diseases worldwide, and their prevalence is continuously rising. Mimp/Mtch2 is a mitochondrial carrier protein homologue, which localizes to the mitochondria and induces mitochondrial depolarization. Mimp/Mtch2 single-nucleotide polymorphism is associated with obesity in humans and its loss in mice muscle protects from obesity. Our aim was to study the effects of Mimp/Mtch2 overexpression in vivo.MethodsTransgenic mice overexpressing Mimp/Mtch2-GFP were characterized and monitored for lipid accumulation, weight and blood glucose levels. Transgenic mice liver and kidneys were used for gene expression analysis.ResultsMimp/Mtch2-GFP transgenic mice express high levels of fatty acid synthase and of beta-oxidation genes and develop fatty livers and kidneys. Moreover, high-fat diet-fed Mimp/Mtch2 mice exhibit high blood glucose levels. Our results also show that Mimp/Mtch2 is involved in lipid accumulation and uptake in cells and perhaps in human obesity.ConclusionsMimp/Mtch2 alters lipid metabolism and may play a role in the onset of obesity and development of insulin resistance.