Ezetimibe as a potential treatment for non-alcoholic fatty liver disease: is the intestine a modulator of hepatic insulin sensitivity and hepatic fat accumulation?
Non-alcoholic fatty liver disease (NAFLD) is the hepatic component of the metabolic syndrome and is known to be associated with marked insulin resistance and increased risk of cardiovascular disease. Ezetimibe, an inhibitor of intestinal cholesterol absorption, inhibits Niemann-Pick C1-like 1 (NPC1L1). Interestingly, NPC1L1 is abundantly expressed in human liver, as well as in the intestine. Recent reports suggest a potential benefit of ezetimibe in improving hepatic insulin sensitivity and decreasing hepatic inflammation and lipid accumulation. Insulin resistance and excess hepatic fat accumulation are regarded as key factors in the pathogenesis of NAFLD. We suggest, therefore, that urgent studies are needed to assess the potential therapeutic benefit of ezetimibe in treating NAFLD.
Ahmed
Mohamed H
MH
Chemical Pathology Department, Southampton University Hospital NHS Trust, Southampton SO16 6YD, UK.
Byrne
Christopher D
CD
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001384:Azetidines / Q000494:pharmacology / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000209:etiology; D000069438:Ezetimibe; D005234:Fatty Liver / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000209:etiology; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics; D026901:Membrane Transport Proteins
D000924:Anticholesteremic Agents; D001384:Azetidines; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D000069438:Ezetimibe