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.