Nature Communications
Abstract
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 Ser86phosphorylation site of acetyltransferaseTip60(Tip60SA/SA) display remarkably reduced body fat mass, andTip60SA/SAfemales 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 inSaccharomyces cerevisiaereveals a requirement of ESA1, yeast ortholog of Tip60, in TAG accumulation. These findings uncover a conserved mechanism linking fatty acid sensing to fat synthesis.
| 论文编号: | DOI:10.1038/s41467-018-04363-w |
| 论文题目: | Tip60-mediated Lipin 1 Acetylation and ER Translocation Determine Triacylglycerol Synthesis Rate |
| 英文论文题目: | Tip60-mediated Lipin 1 Acetylation and ER Translocation Determine Triacylglycerol Synthesis Rate |
| 第一作者: | Terytty Yang Li, Lintao Song, Yu Sun, Jingyi Li, Cong Yi, Sin Man Lam, Dijin Xu, Linkang Zhou, Xiaotong Li, Ying Yang, Chen-Song Zhang, Changchuan Xie, Xi Huang, Guanghou Shui, Shu-Yong Lin, Karen Reue & Sheng-Cai Lin |
| 英文第一作者: | Terytty Yang Li, Lintao Song, Yu Sun, Jingyi Li, Cong Yi, Sin Man Lam, Dijin Xu, Linkang Zhou, Xiaotong Li, Ying Yang, Chen-Song Zhang, Changchuan Xie, Xi Huang, Guanghou Shui, Shu-Yong Lin, Karen Reue & Sheng-Cai Lin |
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| 发表年度: | 2018-06-15 |
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| 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 Ser86phosphorylation site of acetyltransferaseTip60(Tip60SA/SA) display remarkably reduced body fat mass, andTip60SA/SAfemales 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 inSaccharomyces cerevisiaereveals a requirement of ESA1, yeast ortholog of Tip60, in TAG accumulation. These findings uncover a conserved mechanism linking fatty acid sensing to fat synthesis. |
| 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 Ser86phosphorylation site of acetyltransferaseTip60(Tip60SA/SA) display remarkably reduced body fat mass, andTip60SA/SAfemales 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 inSaccharomyces cerevisiaereveals a requirement of ESA1, yeast ortholog of Tip60, in TAG accumulation. These findings uncover a conserved mechanism linking fatty acid sensing to fat synthesis. |
| 刊物名称: | Nature Communications |
| 英文刊物名称: | Nature Communications |
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| 其它备注: | Terytty Yang Li, Lintao Song, Yu Sun, Jingyi Li, Cong Yi, Sin Man Lam, Dijin Xu, Linkang Zhou, Xiaotong Li, Ying Yang, Chen-Song Zhang, Changchuan Xie, Xi Huang, Guanghou Shui, Shu-Yong Lin, Karen Reue & Sheng-Cai Lin. Tip60-mediated Lipin 1 Acetylation and ER Translocation Determine Triacylglycerol Synthesis Rate. Nature Communications. DOI:10.1038/s41467-018-04363-w |
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