J Clin Invest. 2020 Jun 1;130(6):2809-2810. doi: 10.1172/JCI137050.
Hepatic de novo lipogenesis is a major contributor to nonalcoholic fatty liver disease (NAFLD). In this issue of the JCI, Liu and Lin et al. identified Slug as an epigenetic regulator of lipogenesis. Their findings suggest that Slug is stabilized by insulin signaling, and that it promotes lipogenesis by recruiting the histone demethylase Lsd1 to the fatty acid synthase gene promoter. On the other hand, genetic deletion or acute depletion of Slug, or Lsd1 inhibition, reduced lipogenesis and protected against obesity-associated NAFLD and insulin resistance in mice. This study advances our understanding of how lipogenesis is regulated downstream of insulin signaling in health and disease.
肝脏从头合成脂肪是导致非酒精性脂肪性肝病（NAFLD）的主要原因。在本期 JCI 中，Liu 和 Lin 等人发现 Slug 是脂肪生成的表观遗传调节剂。他们的研究结果表明，Slug 受胰岛素信号稳定，通过招募组蛋白去甲基化酶 LSD1 到脂肪酸合成酶基因启动子，促进脂肪生成。另一方面，Slug 或 LSD1 的基因缺失或急性耗竭，或 LSD1 抑制，可减少脂肪生成，并可预防肥胖相关的 NAFLD 和胰岛素抵抗。这项研究增进了我们对健康和疾病中胰岛素信号下游脂肪生成如何受到调控的理解。
