The CYP4/20-HETE/GPR75 axis in the progression of metabolic dysfunction-associated steatosis liver disease (MASLD) to chronic liver disease

These results indicate that the <i>CYP4A11</i> and subsequent <i>GPR75</i> genes are coordinately regulated in the progression of MASLD and may have multiple roles, including 20-HETE activation of peroxisome proliferator-activated receptor α (PPARα) in steatosis and GPR75 in CLD through either increased cell proliferation or vasoconstriction in portal hypertension during cirrhosis. The abrupt reduction in <i>CYP4A11</i> and <i>GPR75</i> in patients with cirrhosis may also be due to increased 20-HETE, serving as a feedback mechanism via <i>GPR75</i>, leading to reduced <i>CYP4A11</i> and <i>GPR75</i> gene expression. This work illustrates key correlations associated with the CYP4/20-HETE/GPR75 axis and the progression of liver disease in humans.