Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhang Zhidong Road, Wuhan 430060, China.
Biomolecules. 2022 Aug 5;12(8):1079. doi: 10.3390/biom12081079.
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis, insulin resistance, mitochondrial dysfunction, inflammation, and oxidative stress. As a group of NAD+-dependent III deacetylases, the sirtuin (SIRT1-7) family plays a very important role in regulating mitochondrial biogenesis and participates in the progress of NAFLD. SIRT family members are distributed in the nucleus, cytoplasm, and mitochondria; regulate hepatic fatty acid oxidation metabolism through different metabolic pathways and mechanisms; and participate in the regulation of mitochondrial energy metabolism. SIRT1 may improve NAFLD by regulating ROS, PGC-1α, SREBP-1c, FoxO1/3, STAT3, and AMPK to restore mitochondrial function and reduce steatosis of the liver. Other SIRT family members also play a role in regulating mitochondrial biogenesis, fatty acid oxidative metabolism, inflammation, and insulin resistance. Therefore, this paper comprehensively introduces the role of SIRT family in regulating mitochondrial biogenesis in the liver in NAFLD, aiming to further explain the importance of SIRT family in regulating mitochondrial function in the occurrence and development of NAFLD, and to provide ideas for the research and development of targeted drugs. Relatively speaking, the role of some SIRT family members in NAFLD is still insufficiently clear, and further research is needed.
非酒精性脂肪性肝病（NAFLD）的特征为肝脂肪变性、胰岛素抵抗、线粒体功能障碍、炎症和氧化应激。作为一组 NAD+依赖的 III 去乙酰化酶，沉默调节蛋白（SIRT1-7）家族在调节线粒体生物发生中起着非常重要的作用，并参与 NAFLD 的进展。SIRT 家族成员分布于核、胞质和线粒体；通过不同的代谢途径和机制调节肝脏脂肪酸氧化代谢；并参与调节线粒体能量代谢。SIRT1 可能通过调节 ROS、PGC-1α、SREBP-1c、FoxO1/3、STAT3 和 AMPK 来改善 NAFLD，从而恢复线粒体功能并减少肝脏脂肪变性。其他 SIRT 家族成员也在调节线粒体生物发生、脂肪酸氧化代谢、炎症和胰岛素抵抗中发挥作用。因此，本文全面介绍了 SIRT 家族在调节 NAFLD 中肝脏线粒体生物发生中的作用，旨在进一步解释 SIRT 家族在调节线粒体功能在 NAFLD 的发生和发展中的重要性，并为靶向药物的研究和开发提供思路。相对而言，一些 SIRT 家族成员在 NAFLD 中的作用尚不够明确，需要进一步研究。
