Department of Pathology, Shanghai Fifth People's Hospital, Fudan University, Shanghai 200240, China.
Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Prostaglandins Other Lipid Mediat. 2022 Dec;163:106671. doi: 10.1016/j.prostaglandins.2022.106671. Epub 2022 Aug 24.
Activation of hepatic stellate cells (HSCs) is generally recognized as a central driver of liver fibrosis. Metabolism of fatty acids (FA) plays a critical role in the activation of HSCs. Proteomics analysis on lysine acetylation of proteins in activated HSCs in our previous study indicated that acetylation of the lysine residues on ACSF2 is one of the most significantly upregulated sites in activated-HSCs and K179 is its important acetylation site. However, the role of acetylation at K179 of ACSF2 on activation of HSCs and free fatty acids (FFA) metabolism remains largely unknown. The reported study demonstrates that acetylation at K179 of ACSF2 promoted HSCs activation. The targeted lipidomic analysis indicated K179 acetylation of ACSF2 mainly affected long chain fatty acids (LCFA) metabolism, especially oleic acid, elaidic acid and palmitoleic acid. And the liquid chromatography mass spectrometry (LC-MS) analysis further demonstrated the formation of many long-chain acyl-CoAs were catalyzed by acetylation at K179 of ACSF2 including oleic acid, elaidic acid and palmitoleic acid. In conclusion, this study indicated that ACSF2 may be a potential therapeutic targets by regulating the metabolism of LCFA for liver fibrosis.
肝星状细胞（HSCs）的激活通常被认为是肝纤维化的核心驱动因素。脂肪酸（FA）的代谢在 HSCs 的激活中起着关键作用。在我们之前的研究中，对激活的 HSCs 中蛋白质赖氨酸乙酰化的蛋白质组学分析表明，ACSF2 赖氨酸残基的乙酰化是激活-HSCs 中上调最显著的位点之一，K179 是其重要的乙酰化位点。然而，ACSF2 上 K179 的乙酰化在 HSCs 激活和游离脂肪酸（FFA）代谢中的作用在很大程度上仍不清楚。本研究表明，ACSF2 上 K179 的乙酰化促进了 HSCs 的激活。靶向脂质组学分析表明，ACSF2 上 K179 的乙酰化主要影响长链脂肪酸（LCFA）代谢，特别是油酸、反油酸和棕榈油酸。LC-MS 分析进一步证明了许多长链酰基辅酶 A 的形成是由 ACSF2 上 K179 的乙酰化催化的，包括油酸、反油酸和棕榈油酸。总之，这项研究表明，ACSF2 可能通过调节 LCFA 的代谢成为治疗肝纤维化的潜在治疗靶点。
