Insulin action suppresses CYP8B1 activity; however, insulin resistance causes the ratio of 12-alpha to non-12alpha hydroxylated bile acids to increase.53 After 20 weeks of an HFD, this ratio was much higher in LCR rats than HCR rats, consistent with our previous observation of worsening metabolic health and reduced insulin signaling in LCR rats on a chronic HFD.6 There was no significant difference in 12-alpha to non-12-alpha hydroxylated bile acids in the 1-week study, suggesting that initial insulin signaling differences between the strains are not a factor. This evidence concerns the gene CYP8B1 and Insulin resistance.