Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism.
Ccdc3: A New P63 Target Involved in Regulation Of Liver Lipid Metabolism.
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CCDC3：一个新的P63靶标参与调节肝脂质代谢。
DOI：
10.1038/s41598-017-09228-8
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发表时间：
2017-08-21
影响因子：
4.6
通讯作者：
Lu H
中科院分区：
文献类型：
--
作者：
Liao W;Liu H;Zhang Y;Jung JH;Chen J;Su X;Kim YC;Flores ER;Wang SM;Czarny-Ratajczak M;Li W;Zeng SX;Lu H
TAp63, a member of the p53 family, has been shown to regulate energy metabolism. Here, we report coiled coil domain-containing 3 (CCDC3) as a new TAp63 target. TAp63, but not ΔNp63, p53 or p73, upregulates CCDC3 expression by directly binding to its enhancer region. The CCDC3 expression is markedly reduced in TAp63-null mouse embryonic fibroblasts and brown adipose tissues and by tumor necrosis factor alpha that reduces p63 transcriptional activity, but induced by metformin, an anti-diabetic drug that activates p63. Also, the expression of CCDC3 is positively correlated with TAp63 levels, but conversely with ΔNp63 levels, during adipocyte differentiation. Interestingly, CCDC3, as a secreted protein, targets liver cancer cells and increases long chain polyunsaturated fatty acids, but decreases ceramide in the cells. CCDC3 alleviates glucose intolerance, insulin resistance and steatosis formation in transgenic CCDC3 mice on high-fat diet (HFD) by reducing the expression of hepatic PPARγ and its target gene CIDEA as well as other genes involved in de novo lipogenesis. Similar results are reproduced by hepatic expression of ectopic CCDC3 in mice on HFD. Altogether, these results demonstrate that CCDC3 modulates liver lipid metabolism by inhibiting liver de novo lipogenesis as a downstream player of the p63 network.
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影响因子：
9
作者：
Lee P;Hock AK;Vousden KH;Cheung EC
通讯作者：
Cheung EC
影响因子：
4.8
作者：
Azad, Abul Kalarn;Chakrabarti, Subhadeep;Fu, YangXin
通讯作者：
Fu, YangXin
异位脂肪、胰岛素抵抗和非酒精性脂肪肝对心血管疾病的影响
DOI：
10.1161/atvbaha.114.303034
发表时间：
2014-06-01
影响因子：
8.7
作者：
Byrne, Christopher D.;Targher, Giovanni
通讯作者：
Targher, Giovanni
影响因子：
64.8
作者：
Herzig, S;Hedrick, S;Montminy, M
通讯作者：
Montminy, M
影响因子：
64.8
作者：
Mills, AA;Zheng, BH;Bradley, A
通讯作者：
Bradley, A