Insulin resistance produces several lithogenic effects; that is, it increases the activity of the rate-limiting step in cholesterol synthesis, hydroxyl-methyl-glutaryl coenzyme A reductase91; modulates the expression of theABCG5 andABCG8 genes involved in the expression of cholesterol transporters (governing biliary cholesterol secretion); and dysregulates the liver transcription factor forkhead box protein O1 (FOXO1)94, which modulates cholesterol homeostasis and high-density lipoprotein (HDL)-mediated reverse cholesterol transport to the liver98. Here, FOXO1 is linked to Insulin resistance.