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首页> 外文期刊>Genes to cells : >Obesity and metabolic syndrome in histone demethylase JHDM2a-deficient mice
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Obesity and metabolic syndrome in histone demethylase JHDM2a-deficient mice

机译：组蛋白脱甲基酶JHDM2a缺陷小鼠的肥胖和代谢综合征

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Histone H3 lysine 9 (H3K9) methylation is a crucial epigenetic mark of heterochromatin formation and transcriptional silencing. Recent studies demonstrated that most covalent histone lysine modifications are reversible and the jumonji C (JmjC)-domain-containing proteins have been shown to possess such demethylase activities. However, there is little information available on the biological roles of histone lysine demethylation in intact animal model systems. JHDM2A (JmjC-domain-containing histone demethylase 2A, also known as JMJD1A) catalyses removal of H3K9 mono- and dimethylation through iron and l-ketoglutarate dependent oxidative reactions. Here, we demonstrate that JHDM2a also regulates metabolic genes related to energy homeostasis including anti-adipogenesis, regulation of fat storage, glucose transport and type 2 diabetes. Mice deficient in JHDM2a (JHDM2a-/-) develop adult onset obesity, hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia and hyperleptinemia, which are hallmarks of metabolic syndrome. JHDM2a-/- mice furthermore exhibit fasted induced hypothermia indicating reduced energy expenditure and also have a higher respiratory quotient indicating less fat utilization for energy production. These observations may explain the obesity phenotype in these mice. Thus, H3K9 demethylase JHDM2a is a crucial regulator of genes involved in energy expenditure and fat storage, which suggests it is a previously unrecognized key regulator of obesity and metabolic syndrome.
机译：组蛋白H3赖氨酸9（H3K9）甲基化是异染色质形成和转录沉默的重要表观遗传标志。最近的研究表明，大多数共价的组蛋白赖氨酸修饰是可逆的，并且已证明含有jumonji C（JmjC）域的蛋白质具有这种脱甲基酶活性。但是，关于完整组动物模型系统中组蛋白赖氨酸脱甲基化的生物学作用的信息很少。 JHDM2A（含JmjC域的组蛋白脱甲基酶2A，也称为JMJD1A）通过铁和1-酮戊二酸依赖性氧化反应催化H3K9单和二甲基化的去除。在这里，我们证明JHDM2a还调节与能量稳态相关的代谢基因，包括抗脂肪生成，脂肪储存调节，葡萄糖转运和2型糖尿病。缺乏JHDM2a（JHDM2a-/-）的小鼠会发展成年肥胖，高甘油三酯血症，高胆固醇血症，高胰岛素血症和高瘦素血症，这是代谢综合征的标志。此外，JHDM2a-/-小鼠表现出禁食引起的体温过低，表明能量消耗减少，并且呼吸商较高，表明脂肪产生的脂肪利用较少。这些观察结果可以解释这些小鼠的肥胖表型。因此，H3K9脱甲基酶JHDM2a是涉及能量消耗和脂肪储存的基因的关键调节剂，这表明它是肥胖和代谢综合征先前未被认识的关键调节剂。

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