lesterol metabolism. Now we know where NPC1L1 is and what it is doing in the liver. Of course, we now want to know more. Several questions remain to be answered. Given the importance of NPC1L1 for systemic cholesterol metabolism, it is easily predictable that its function is highly regulated. Besides the putative repressive role of LXR and peroxisome proliferator-activated receptor alpha (PPAR␣) on intestinal NPC1L1 transcription, 16,17 very little is known at the present time on the regulation of NPC1L1 expression and activity. Because NPC1L1 restricts cholesterol disposal both in the liver and in the intestine, it is reasonable to assume that the same sensor might be responsible for NPC1L1 regulation in the 2 anatomical districts. Alternatively, hormonal signals carried in the bloodstream or in bile could synchronize the regulation of NPC1L1 in the gut-liver axis. A last question would be on the long-term effect of blocking cholesterol "absorption" in the human canaliculus via ezetimibe with the subsequent increase in biliary cholesterol concentration. Would ezetimibe increase the cholesterol saturation index in bile, thus predisposing a patient to cholesterol gallstone formation and atherosclerosis of the bile ducts? Studies in this direction are urgently needed.
Identification of Resident Hepatic Stem Cell PopulationsSchmelzer E, Zhang L, Bruce A, Wauthier E, Ludlow J, Yao H, Moss N, Melhem A, McClelland R, Turner W, Kulik M, Sherwood S, Tallheden T, Cheng N, Furth ME, Reid LM