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DOI | 10.1038/s41467-019-11990-4 |
Tip60-mediated lipin 1 acetylation and ER translocation determine triacylglycerol synthesis rate | |
Li, Terytty Yang1; Song, Lintao1; Sun, Yu1; Li, Jingyi1; Yi, Cong2; Lam, Sin Man3; Xu, Dijin4,5; Zhou, Linkang4,5; Li, Xiaotong1; Yang, Ying1; Zhang, Chen-Song1; Xie, Changchuan1; Huang, Xi1; Shui, Guanghou3; Lin, Shu-Yong1; Reue, Karen6; Lin, Sheng-Cai1 | |
2019-09-09 | |
发表期刊 | NATURE COMMUNICATIONS |
ISSN | 2041-1723 |
出版年 | 2018 |
卷号 | 9 |
文章类型 | Article |
语种 | 英语 |
国家 | Peoples R China; USA |
英文摘要 | Obesity is characterized by excessive fatty acid conversion to triacylglycerols (TAGs) in adipose tissues. However, how signaling networks sense fatty acids and connect to the stimulation of lipid synthesis remains elusive. Here, we show that homozygous knock-in mice carrying a point mutation at the Ser(86) phosphorylation site of acetyltransferase Tip60 (Tip60(SA/SA)) display remarkably reduced body fat mass, and Tip60(SA/SA) females fail to nurture pups to adulthood due to severely reduced milk TAGs. Mechanistically, fatty acids stimulate Tip60-dependent acetylation and endoplasmic reticulum translocation of phosphatidic acid phosphatase lipin 1 to generate diacylglycerol for TAG synthesis, which is repressed by deacetylase Sirt1. Inhibition of Tip60 activity strongly blocks fatty acid-induced TAG synthesis while Sirt1 suppression leads to increased adiposity. Genetic analysis of loss-of-function mutants in Saccharomyces cerevisiae reveals a requirement of ESA1, yeast ortholog of Tip60, in TAG accumulation. These findings uncover a conserved mechanism linking fatty acid sensing to fat synthesis. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000432115300020 |
WOS关键词 | PHOSPHATIDIC-ACID PHOSPHATASE ; ADIPOSE-TISSUE ; SACCHAROMYCES-CEREVISIAE ; ACETYLTRANSFERASE TIP60 ; INSULIN-RESISTANCE ; MILK LIPIDS ; DNA-DAMAGE ; OBESITY ; PHOSPHORYLATION ; METABOLISM |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/204528 |
专题 | 资源环境科学 |
作者单位 | 1.Xiamen Univ, Sch Life Sci, Innovat Ctr Cell Signaling Network, State Key Lab Cellular Stress Biol, Xiamen 361102, Fujian, Peoples R China; 2.Zhejiang Univ, Sch Basic Med Sci, Hangzhou 310058, Zhejiang, Peoples R China; 3.Chinese Acad Sci, Inst Genet & Dev Biol, State Key Lab Mol Dev Biol, Beijing 100084, Peoples R China; 4.Tsinghua Univ, Sch Life Sci, MOE Key Lab Bioinformat, Beijing 100084, Peoples R China; 5.Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China; 6.Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA |
推荐引用方式 GB/T 7714 | Li, Terytty Yang,Song, Lintao,Sun, Yu,et al. Tip60-mediated lipin 1 acetylation and ER translocation determine triacylglycerol synthesis rate[J]. NATURE COMMUNICATIONS,2019,9. |
APA | Li, Terytty Yang.,Song, Lintao.,Sun, Yu.,Li, Jingyi.,Yi, Cong.,...&Lin, Sheng-Cai.(2019).Tip60-mediated lipin 1 acetylation and ER translocation determine triacylglycerol synthesis rate.NATURE COMMUNICATIONS,9. |
MLA | Li, Terytty Yang,et al."Tip60-mediated lipin 1 acetylation and ER translocation determine triacylglycerol synthesis rate".NATURE COMMUNICATIONS 9(2019). |
条目包含的文件 | 条目无相关文件。 |
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