Vitamin C Inhibits the Metabolic Changes Induced by Tet1 Insufficiency Under High Fat Diet Stress
Vitamin C Inhibits the Metabolic Changes Induced by Tet1 Insufficiency Under High Fat Diet Stress
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维生素 C 抑制高脂饮食压力下 Tet1 不足引起的代谢变化
DOI：
10.1002/mnfr.202100417
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发表时间：
2021
影响因子：
5.2
通讯作者：
Zheng Ling
中科院分区：
文献类型：
--
作者：
Yuan Yangmian;Liu Chengyu;Chen Xingrui;Sun Yuyan;Xiong Mingrui;Fan Yu;Petersen Robert B.;Chen Hong;Huang Kun;Zheng Ling
ScopeDNA甲基化导致肥胖，但DNA去甲基化酶10 - 11易位蛋白1（Tet 1）在肥胖中的作用仍不清楚。维生素C是蛋白质的泰特家族的辅因子，但维生素C是否可以用于治疗肥胖症通过Tet1.Methods和ResultsTet 1 +/+和Tet 1 +/−小鼠喂养高脂肪饮食（HFD）有待澄清。Tet 1 +/−小鼠的白色脂肪组织和肝脏中发现了更高的体重增加和更严重的肝脏脂肪变性，并伴有5-羟甲基胞嘧啶（5 hmC）水平降低。在棕榈酸或油酸处理的Tet 1 +/−小鼠原代肝细胞中观察到脂质蓄积，Tet 1过表达或维生素C处理可挽救这些肝细胞。亚硫酸氢盐测序显示Tet 1 +/−小鼠肝脏中脂解相关基因的DNA甲基化水平较高。值得注意的是，口服维生素C正常化的DNA甲基化水平，促进脂解，并减少肥胖HFD-fedTet 1 +/-mice.ConclusionsThe结果揭示了一种新的功能Tet 1在肥胖症和提供了一个新的机制，通过增强Tet 1活性的有益作用，维生素C在代谢疾病。
ScopeDNA methylation contributes to obesity, but the role of the DNA demethylase ten‐eleven translocation protein 1 (Tet1) in obesity remains unclear. Vitamin C is a cofactor for the Tet family of proteins, but whether vitamin C can be used to treat obesity via Tet1 awaits clarification.Methods and ResultsTet1+/+andTet1+/−mice are fed a high fat diet (HFD). Higher weight gain and more severe hepatic steatosis, accompanied by reduced 5‐hydromethylcytosine (5hmC) levels, are found in the white adipose tissue and liver ofTet1+/−mice. Accumulated lipids are observed in palmitic acid or oleic acid treated primary hepatocytes derived fromTet1+/−mice, which are rescued by Tet1 overexpression or vitamin C treatment. Bisulfite sequencing reveals higher DNA methylation levels on lipolysis related genes in the liver ofTet1+/−mice. Notably, oral intake of vitamin C normalizes DNA methylation levels, promotes lipolysis, and decreases obesity in HFD‐fedTet1+/−mice.ConclusionsThe results reveal a novel function of Tet1 in obesity and provide a new mechanism for the beneficial role of vitamin C in metabolic diseases through enhanced Tet1 activity.