Bile acid levels in the enterohepatic circulation are under tight negative feedback control, mainly achieved through transcriptional control of bile acid synthetic enzymes involving farnesoid X receptor (FXR) (6) (Fig. 2). Liver X receptor (LXR) is a master regulator of a feed-forward mechanism that helps to maintain cholesterol homeostasis. On activation by oxysterols, LXR forms heterodimers with the retinoid X receptor, which induce the expression of several genes that facilitate intestinal sterol excretion and reverse cholesterol transport. In the liver, 7-hydroxylation of cholesterol is regulated in an LXR-dependent manner, thereby increasing bile acid synthesis. However, humans do not respond with upregulation of CYP7A1 in response to excess dietary cholesterol, probably attributable to the absence of an LXR-responsive element in the CYP7A1 promoter (1).