5αRs catalyse the first step in cortisol clearance towards 5α-tetrahydrocortisol formation, and 5αR1–/– mice have increased hepatic steatosis on a Western diet (Dowman et al. 2013, Livingstone et al. 2015), whilst patients treated with 5αR inhibitors have increased intrahepatic lipid accumulation (Hazlehurst et al. 2016), skeletal muscle insulin resistance (Upreti et al. 2014) and risk of type 2 diabetes (Wei et al. 2019). This evidence concerns the gene INS and fatty liver disease.