Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease without specific Food and Drug Administration-approved drugs. Recent advances suggest that chromatin remodeling and epigenetic alteration contribute to the development of NAFLD. The functions of the corresponding molecular modulator in NAFLD, however, are still elusive. commonly known as lysine-specific histone demethylase 1, has been reported to increase glucose uptake in hepatocellular carcinoma. In addition, a recent study suggests that inhibition of reduces lipid accumulation in primary brown adipocytes. We here investigated the role of , one of the most important histone demethylases, in NAFLD. In this study, we observed a significant upregulation of in NAFLD mice, monkeys, and humans compared to the control group. Based on these results, we further found that the can exacerbate lipid accumulation and inflammation in hepatocytes and mice. Mechanistically, exerted its effects by elevating chromatin accessibility, subsequently promoting the development of NAFLD. Furthermore, the mutation of blunted its capability to promote the development of NAFLD. In summary, our study discovered that exacerbates hepatic steatosis and inflammation in NAFLD via increasing chromatin accessibility, further indicating the importance of harnessing chromatin remodeling and epigenetic alteration in combating NAFLD. might be considered as a potential therapeutic target in this regard.

中文翻译：

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组蛋白去甲基化酶 KDM1A 通过增加 NAFLD 中染色质的可及性来促进肝脏脂肪变性和炎症

非酒精性脂肪性肝病（NAFLD）是最常见的慢性肝病，没有特定的食品和药物管理局批准的药物。最近的进展表明染色质重塑和表观遗传改变有助于 NAFLD 的发展。然而，NAFLD 中相应分子调节剂的功能仍然难以捉摸。据报道，通常称为赖氨酸特异性组蛋白去甲基化酶 1，可增加肝细胞癌中的葡萄糖摄取。此外，最近的一项研究表明，抑制可减少原代棕色脂肪细胞中的脂质积累。我们在这里研究了最重要的组蛋白去甲基化酶之一在 NAFLD 中的作用。在这项研究中，我们观察到与对照组相比，NAFLD 小鼠、猴子和人类的 β2 显着上调。基于这些结果，我们进一步发现它会加剧肝细胞和小鼠的脂质积累和炎症。从机制上讲，通过提高染色质可及性发挥其作用，从而促进 NAFLD 的发展。此外，突变削弱了其促进 NAFLD 发展的能力。总之，我们的研究发现，通过增加染色质可及性，加剧 NAFLD 中的肝脏脂肪变性和炎症，进一步表明利用染色质重塑和表观遗传改变在对抗 NAFLD 中的重要性。在这方面可能被认为是一个潜在的治疗靶点。