Hepatocyte Sirtuin 6 Protects against Atherosclerosis and Steatohepatitis by Regulating Lipid Homeostasis.
Hepatocyte Sirtuin 6 Protects against Atherosclerosis and Steatohepatitis by Regulating Lipid Homeostasis.
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肝细胞糖蛋白6通过调节脂质稳态来保护动脉粥样硬化和脂肪性肝炎。
DOI：
10.3390/cells12152009
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发表时间：
2023-08-05
期刊：
影响因子：
6
通讯作者：
Zhang, Yanqiao
中科院分区：
文献类型：
--
作者：
Zhu, Yingdong;Hu, Shuwei;Pan, Xiaoli;Gopoju, Raja;Bawa, Fathima Cassim N.;Yin, Liya;Xu, Yanyong;Zhang, Yanqiao
组蛋白去乙酰化酶Sirtuin 6（SIRT 6）调节许多生物学过程。已知SIRT 6调节肝脏脂质代谢并抑制非酒精性脂肪性肝病（NAFLD）的发展。我们的目的是研究肝细胞SIRT 6在动脉粥样硬化发展中的作用，并进一步表征SIRT 6对NAFLD作用的机制。过度表达或缺乏肝细胞SIRT 6的Ldlr−/−小鼠被喂食西方饮食16周。研究了肝脏SIRT 6在非酒精性脂肪性肝炎（NASH）、动脉粥样硬化和肥胖症的发展中的作用。我们还研究了p53是否参与过表达肝脏SIRT 6的小鼠NAFLD的发病机制。我们的数据表明，肝细胞SIRT 6的缺失加重了Ldlr−/−小鼠NAFLD、动脉粥样硬化和肥胖的发展，而腺相关病毒（AAV）介导的肝脏中人SIRT 6的过表达具有相反的作用。从机制上讲，肝细胞SIRT 6可能通过抑制脂肪生成、脂滴形成和p53信号传导来抑制NAFLD的发展。肝细胞SIRT 6也可能通过抑制肠道脂质吸收和肝脏VLDL分泌来抑制动脉粥样硬化的发展。肝脏SIRT 6也增加了能量消耗。总之，我们的数据表明，肝细胞SIRT 6通过调节肝脏和肠道中的脂质代谢来防止动脉粥样硬化，NAFLD和肥胖。
Histone deacetylase Sirtuin 6 (SIRT6) regulates many biological processes. SIRT6 is known to regulate hepatic lipid metabolism and inhibit the development of nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the role of hepatocyte SIRT6 in the development of atherosclerosis and further characterize the mechanism underlying SIRT6’s effect on NAFLD. Ldlr−/− mice overexpressing or lacking hepatocyte SIRT6 were fed a Western diet for 16 weeks. The role of hepatic SIRT6 in the development of nonalcoholic steatohepatitis (NASH), atherosclerosis, and obesity was investigated. We also investigated whether p53 participates in the pathogenesis of NAFLD in mice overexpressing hepatic SIRT6. Our data show that loss of hepatocyte SIRT6 aggravated the development of NAFLD, atherosclerosis, and obesity in Ldlr−/− mice, whereas adeno-associated virus (AAV)-mediated overexpression of human SIRT6 in the liver had opposite effects. Mechanistically, hepatocyte SIRT6 likely inhibited the development of NAFLD by inhibiting lipogenesis, lipid droplet formation, and p53 signaling. Hepatocyte SIRT6 also likely inhibited the development of atherosclerosis by inhibiting intestinal lipid absorption and hepatic VLDL secretion. Hepatic SIRT6 also increased energy expenditure. In conclusion, our data indicate that hepatocyte SIRT6 protects against atherosclerosis, NAFLD, and obesity by regulating lipid metabolism in the liver and intestine.
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影响因子：
25.7
作者：
Derdak, Zoltan;Villegas, Kristine A.;Harb, Ragheb;Wu, Annie M.;Sousa, Aryanna;Wands, Jack R.
通讯作者：
Wands, Jack R.
影响因子：
13.8
作者：
Kugel, Site;Mostoslavsky, Raul
通讯作者：
Mostoslavsky, Raul
影响因子：
4.2
作者：
通讯作者：
--
Sirt6 在肥胖和糖尿病中的作用。
影响因子：
4
作者：
Kuang J;Chen L;Tang Q;Zhang J;Li Y;He J
通讯作者：
He J
影响因子：
--
作者：
Zhang, Yanqiao;Ge, Xuemei;Novak, Colleen M.
通讯作者：
Novak, Colleen M.