JMJD2B/KDM4B inactivation in adipose tissues accelerates obesity and systemic metabolic abnormalities
JMJD2B/KDM4B inactivation in adipose tissues accelerates obesity and systemic metabolic abnormalities
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DOI：
10.1111/gtc.12627
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发表时间：
2018-09-01
期刊：
影响因子：
2.1
通讯作者：
Okada, Hitoshi
中科院分区：
文献类型：
--
作者：
Kang, Changkeun;Saso, Kayoko;Okada, Hitoshi
肥胖是一个严重的全球性健康问题;然而，遗传学和表观遗传学在肥胖发生和发展中的作用仍然没有完全了解。本研究的目的是确定Kdm 4 b，这属于一个亚家族的组蛋白去甲基化酶，在体内脂肪形成和脂肪代谢的作用。我们建立了条件性Kdm 4 b基因敲除小鼠。脂肪细胞中Kdm 4 b的失活（K4 bKO）诱导高脂饮食（HFD）小鼠严重肥胖。HFD喂养的K4 bKO小鼠表现出脂肪量增加和脂肪生成相关基因表达水平升高。相反，参与能量消耗和线粒体功能的基因下调。支持这些发现，Kdm 4 b缺陷细胞的能量消耗显着降低。此外，还观察到葡萄糖耐受不良和肝脂肪变性进展伴肝细胞损伤。这些数据表明，Kdm 4 b是通过增强脂肪细胞中的能量消耗的全身代谢的关键调节剂。
Obesity is a serious global health issue; however, the roles of genetics and epigenetics in the onset and progression of obesity are still not completely understood. The aim of this study was to determine the role of Kdm4b, which belongs to a subfamily of histone demethylases, in adipogenesis and fat metabolism in vivo. We established conditional Kdm4b knockout mice. Inactivation of Kdm4b in adipocytes (K4bKO) induced profound obesity in mice on a high fat diet (HFD). The HFD-fed K4bKO mice exhibited an increased volume of fat mass and higher expression levels of adipogenesis-related genes. In contrast, the genes involved in energy expenditure and mitochondrial functions were down-regulated. Supporting these findings, the energy expenditure of Kdm4b-deficient cells was markedly decreased. In addition, progression of glucose intolerance and hepatic steatosis with hepatocellular damages was observed. These data indicate that Kdm4b is a critical regulator of systemic metabolism via enhancing energy expenditure in adipocytes.