肝细胞 Sirtuin 6 通过调节脂质平衡来保护抗动脉样硬化和稳肝炎

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Yingdong Zhu^1,2, Shuwei Hu¹, Xiaoli Pan¹

¹Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, OH 44272, USA.

Cells

|August 11, 2023

概括

肝细胞Sirtuin 6 (SIRT6) 能够预防动脉样硬化和非酒精性脂肪性肝病 (NAFLD). 失去SIRT6会使这些情况恶化,而增加SIRT6则通过调节脂质代谢来提供保护.

科学领域:

代谢调节代谢调节代谢调节
脂质代谢脂质代谢是一种
心血管疾病的研究研究.

背景情况:

锡尔图因6 (SIRT6) 是一种参与许多生物过程的基因组脱乙酶.
SIRT6在肝脂代谢中发挥作用,并因其对非酒精性脂肪肝疾病 (NAFLD) 发展的抑制作用而得到认可.
肝细胞SIRT6在动脉样硬化中的确切作用及其在NAFLD的潜在机制需要进一步阐明.

研究的目的:

研究肝细胞SIRT6在动脉样硬化发展中的作用.
进一步描述SIRT6影响NAFLD的机制.
在肝脏SIRT6过度表达的背景下,研究p53在NAFLD病变的参与.

主要方法:

使用Ldlr^-/-小鼠,肝细胞SIRT6表达变化 (过度表达或淘汰).
进行了16周的西方饮食,以评估对NAFLD,动脉样硬化和肥胖的影响.
研究了机械路径,包括脂质生成,脂质滴形成,p53信号传递,肠道脂质吸收和肝脏VLDL分泌.

主要成果:

肝细胞SIRT6的损失在小鼠中加剧了NAFLD,动脉样硬化和肥胖.
通过腺相关病毒 (AAV) 介导的SIRT6在肝脏中的过度表达显示出保护作用.
肝细胞SIRT6通过抑制脂生成,脂滴形成和p53信号传递来抑制NAFLD.
肝细胞SIRT6通过减少肠道脂质吸收和肝脏VLDL分泌来减轻动脉样硬化,同时增加能量消耗.

结论:

肝细胞SIRT6在预防动脉样硬化,NAFLD和肥胖的发展方面发挥着至关重要的保护作用.
在肝脏和肠道中,SIRT6通过调节脂质代谢来发挥其保护作用.
针对肝脏SIRT6可能代表代谢和心血管疾病的治疗策略.

关键词:

这是NAFLD.在Sirtuin 6中使用.动脉样硬化动脉样硬化胆酸胆酸是一种胆酸.脂质新陈代谢脂质新陈代谢肥胖肥胖肥胖肥胖肥胖肥胖肥胖肥胖

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