[2, 3] However, no standard treatment for NAFLD/NASH has been established, except for diet control and exercise at present. To gain a deeper understanding of NAFLD/NASH,

it is necessary to study suitable animal models simulating the pathological changes of human NAFLD/NASH. Thus far, many different animal models of NAFLD/NASH have been reported. Genetic rodent models, such as the leptin-deficient (ob/ob) or leptin-resistant (db/db) mouse, and diet-induced rodent models, such as the dietary methionine/choline-deficient diet model,[4] are two major types of animal models utilized by many research groups. The Fatty Liver Shionogi (FLS) mouse, an inbred strain of mouse originating from the ddN colony, spontaneously PF-02341066 molecular weight develops fatty liver (hepatic steatosis) without marked obesity under a normal diet.[5, 6] We previously reported that glucose tolerance of the FLS mice is impaired, indicating the FLS mice as a clue for clarifying the biological link between NAFLD and diabetes.[7] Our recent study proved that FLS mice demonstrated excessive hepatic triglyceride (TG) accumulation due to impaired very low-density lipoprotein (VLDL) secretion caused by reduced hepatic microsomal TG transfer protein (MTP), and subsequently exhibited selleck compound NASH-comparable hepatic lesions.[8] Several clinical studies revealed that reduced MTP is a key factor distinguishing simple

fatty liver from NASH,[9] and a polymorphism of the MTP gene was shown to be associated with the development of NASH.[10] There is also a clinical report that hepatic mRNA expression of MTP was significantly lower in individuals with NASH than in those with simple fatty liver.[11] Taking these results together, it is likely that reduced hepatic expression of MTP plays an important role in the development of NASH. Ezetimibe is clinically used for the treatment of hypercholesteremia by inhibiting cholesterol absorption.

It was shown to inhibit Niemann–Pick C1 Like 1 (NPC1L1)-dependent cholesterol transport at the brush border of the intestine and in the liver.[12] Recently, in an experimental NAFLD model, ezetimibe monotherapy was shown not Amobarbital only to protect against diet-induced hyperlipidemia, but also to attenuate liver steatosis.[13, 14] Long-term combination therapy with ezetimibe and acarbose, an α-glucosidase inhibitor retarding carbohydrate absorption, significantly increased the expression of MTP and peroxisome proliferator-activated receptor-α (PPAR-α) in the liver, compared with either monotherapy.[15] Additionally, in patients with NASH, hepatic MTP mRNA expression was reported to be significantly increased after ezetimibe treatment, compared to that before.[16] These findings suggest that it is possible that ezetimibe would be effective for treatment of NAFLD/NASH.