Fig. 7.

Proposed mechanism promoting fatty liver to inflammation: Chronic persistent increases in 26-HC and 3β-HCA as shown in this work with StarD1 overexpression, WD feeding, and T2DM models (STZ-treated mice) leads to accumulation of oxysterols and their lipotoxic metabolites, as occurs in humans in the absence of CYP7B1. In early fatty liver, lowered hepatocellular insulin levels due to the insulin-resistant condition suppressed Cyp7b1 gene expression. Interestingly, Ch25h was also repressed in the insulin-resistant condition, leading to lower hepatocellular 25-HC.