Brown Fat Dnmt3b Deficiency Ameliorates Obesity in Female Mice.
Brown Fat Dnmt3b Deficiency Ameliorates Obesity in Female Mice.
复制标题
DOI：
10.3390/life11121325
复制
发表时间：
2021-11-30
期刊：
影响因子：
--
通讯作者：
Shi H
中科院分区：
文献类型：
--
作者：
Li F;Cui X;Jing J;Wang S;Shi H;Xue B;Shi H
肥胖是由于能量摄入超过能量消耗而导致的长期能量失衡。激活棕色脂肪的生热作用已被证明可以对抗肥胖症。表观遗传调控，包括DNA甲基化，已经成为棕色脂肪产热功能的关键调控因素。在这里，我们旨在研究Dnmt3b，一种参与从头DNA甲基化的DNA甲基转移酶，在调节棕色脂肪产热和肥胖中的作用。我们发现，棕色脂肪中Dnmt3b的特异性缺失促进了棕色脂肪中的生热和线粒体程序，增加了能量消耗，并减少了雌性小鼠的肥胖。雌性基因敲除小鼠具有瘦削的表型，也表现出更高的胰岛素敏感性。此外，棕色脂肪中Dnmt3b的缺乏还可以防止雌性小鼠因饮食导致的肥胖和胰岛素抵抗。有趣的是，我们的RNA-seq分析显示，在雌性Dnmt3b基因敲除小鼠的棕色脂肪中，PI3K-Akt通路上调。然而，雄性Dnmt3b基因敲除小鼠的体重没有变化，这表明在棕色脂肪Dnmt3b基因敲除模型中存在性别二型性。结果表明，Dnmt3b在雌性小鼠的棕色脂肪功能、能量代谢和肥胖的调节中起着重要的作用。
Obesity results from a chronic energy imbalance due to energy intake exceeding energy expenditure. Activation of brown fat thermogenesis has been shown to combat obesity. Epigenetic regulation, including DNA methylation, has emerged as a key regulator of brown fat thermogenic function. Here we aimed to study the role of Dnmt3b, a DNA methyltransferase involved in de novo DNA methylation, in the regulation of brown fat thermogenesis and obesity. We found that the specific deletion of Dnmt3b in brown fat promotes the thermogenic and mitochondrial program in brown fat, enhances energy expenditure, and decreases adiposity in female mice fed a regular chow diet. With a lean phenotype, the female knockout mice also exhibit increased insulin sensitivity. In addition, Dnmt3b deficiency in brown fat also prevents diet-induced obesity and insulin resistance in female mice. Interestingly, our RNA-seq analysis revealed an upregulation of the PI3K-Akt pathway in the brown fat of female Dnmt3b knockout mice. However, male Dnmt3b knockout mice have no change in their body weight, suggesting the existence of sexual dimorphism in the brown fat Dnmt3b knockout model. Our data demonstrate that Dnmt3b plays an important role in the regulation of brown fat function, energy metabolism and obesity in female mice.