Figure 4.

Summary figure. sEH inhibitors preserve levels of endogenously produced epFAs by preventing their sEH hydrolysis. sEH inhibition improves disease phenotype in non-alcoholic liver disease, non-alcoholic steatohepatitis, hepatic fibrosis, cirrhotic portal hypertension, and cirrhotic sepsis. Individual epFAs are shown to improve insulin resistance, inflammation, autophagy, oxidative stress, and endoplasmic reticulum stress, suggesting a mechanistic link between sEH inhibitors and protection against liver diseases. Future research should interrogate the efficacy of sEH inhibition in ALD, viral hepatitis, hepatocellular carcinoma, and cholestatic liver disease. PUFAs, polyunsaturated fatty acids; CYP, cytochrome P450 2J/2C families; sEH, soluble epoxide hydrolase; sEHI, soluble epoxide hydrolase inhibitor; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; PTH, portal hypertension; ALD, alcohol-associated liver disease; HCC, hepatocellular carcinoma.