Figure 1.

Proposed core regulatory network motif that controls lipid homeostasis in the liver and is dysregulated during the progression of non-alcoholic fatty liver disease (NAFLD). The motif is composed of two tightly regulated, self-activated pairs of transcription factors (each pair shown in a dotted rectangle): HNF4α/HNF1α (maintaining the hepatocyte cell state) and PPARγ/SREBP-1c (driving an adipocytic cell state and implicated in initiation and progression of NAFLD). The arrows show transcriptional activation, and the solid bars represent transcriptional repression. The relative levels of these proteins in a cell can determine its cell state as hepatocytes in healthy liver, adipocytes in the fat tissue, or steatotic hepatocytes in livers of patients suffering from fatty liver.