5α-Reductase Type 1 Deficiency or Inhibition Predisposes to Insulin Resistance, Hepatic Steatosis, and Liver Fibrosis in Rodents

The study investigated the role of 5α-Reductase type 1 (5αR1) in metabolic syndrome manifestations in the liver using male mice and rats. Male 5αR1 knockout mice on a high-fat diet showed increased weight gain, hyperinsulinemia, and hepatic steatosis compared to controls, with liver profiles indicating decreased fatty acid β-oxidation and increased triglyceride storage. These mice also exhibited a higher susceptibility to liver fibrosis after carbon tetrachloride exposure. Additionally, the 5α-reductase inhibitor finasteride caused hyperinsulinemia and hepatic steatosis in obese Zucker rats, regardless of androgen presence. The findings suggested that 5αR1 deficiency led to insulin resistance and hepatic steatosis, likely due to glucocorticoid accumulation, and increased the risk of liver fibrosis. The study highlighted potential implications for metabolic liver disease progression in obesity and men with prostate disease undergoing nonselective 5α-reductase inhibition.