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Male mice, homozygous for a disrupted 5\u03b1R1 allele (5\u03b1R1 knockout [KO] mice), were studied after metabolic (high-fat diet) and fibrotic (carbon tetrachloride [CCl4]) challenge. The effect of the 5\u03b1-reductase inhibitor finasteride on metabolism was investigated in male obese Zucker rats. While eating a high-fat diet, male 5\u03b1R1-KO mice demonstrated greater mean weight gain (21.6 \u00b1 1.4 vs 16.2 \u00b1 2.4 g), hyperinsulinemia (insulin area under the curve during glucose tolerance test 609 \u00b1 103 vs. 313 \u00b1 66 ng \u22c5 mL\u22121 \u22c5 min), and hepatic steatosis (liver triglycerides 136.1 \u00b1 17.0 vs. 89.3 \u00b1 12.1 \u03bcmol \u22c5 g\u22121). mRNA transcript profiles in liver were consistent with decreased fatty acid \u03b2-oxidation and increased triglyceride storage. 5\u03b1R1-KO male mice were more susceptible to fibrosis after CCl4 administration (37% increase in collagen staining). The nonselective 5\u03b1-reductase inhibitor finasteride induced hyperinsulinemia and hepatic steatosis (10.6 \u00b1 1.2 vs. 7.0 \u00b1 1.0 \u03bcmol \u22c5 g\u22121) in obese male Zucker rats, both intact and castrated. 5\u03b1R1 deficiency induces insulin resistance and hepatic steatosis, consistent with the intrahepatic accumulation of glucocorticoids, and predisposes to hepatic fibrosis. Hepatic steatosis is independent of androgens in rats. Variations in 5\u03b1R1 activity in obesity and with nonselective 5\u03b1-reductase inhibition in men with prostate disease may have important consequences for the onset and progression of metabolic liver disease.<\/jats:p>","DOI":"10.2337\/db14-0249","type":"journal-article","created":{"date-parts":[[2014,9,20]],"date-time":"2014-09-20T01:11:46Z","timestamp":1411175506000},"page":"447-458","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":84,"title":["5\u03b1-Reductase Type 1 Deficiency or Inhibition Predisposes to Insulin Resistance, Hepatic Steatosis, and Liver Fibrosis in Rodents"],"prefix":"10.2337","volume":"64","author":[{"given":"Dawn E.W.","family":"Livingstone","sequence":"first","affiliation":[{"name":"University\/British Heart Foundation Centre for Cardiovascular Science, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, 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