Figure 7.

Proposed model of cholestenoic acid (CA) gene regulation in hepatocytes. A high-sugar diet produces excess of acetyl-CoA, which can be used to synthesize cholesterol and long chain fatty acids. Cholesterol is a precursor for the synthesis for 25-hydroxycholesterol (25HC), 27-hydroxycholesterol (27HC), and CA in mitochondria. These oxysterols bind liver X receptors (LXRs) for transport to the nucleus where they regulate genes involved in calcium-AMPK and fatty acid and cholesterol biosynthetic pathways. 25HC, 27HC, and CA may play different roles in the pathophysiology of nonalcoholic fatty liver disease (NAFLD). Dashed red lines represent known pathways, and the blue solid lines represent the proposed pathways regulated by CA.