Novel Findings for the Development of Drug Therapy for Various Liver Diseases: Liver Microsomal Triglyceride Transfer Protein Activator May Be a Possible Therapeutic Agent in Non-alcoholic Steatohepatitis

摘要

The factors involved in the progression of non-alcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) are not fully understood and thus it is urgently needed to elucidate these factors. Steatosis is not causal in the development of NASH, but rather it sensitizes the liver to the damaging effects of second hits such that stressors innocuous to a healthy liver lead to the development of NASH in the steatotic liver. In the previous study, most of the hepatic lipid metabolite profiles were similar in the NAFL and NASH groups. However, very-low-density lipoprotein (VLDL) synthesis, especially hepatic microsomal triglyceride transfer protein (MTP) mRNA expression, was impaired in the NASH group. Moreover, NASH showed significantly higher incidence of minor alley appearance compared with NAFL, indicating the possibility of association between NASH pathogenesis and decreased congenital MTP activity. MTP is one of the enzymes that transfer triglycerides to nascent apolipoprotein B, producing VLDL and removing lipid from the hepatocyte. A growing body of literature suggests that the measurement of hepatic MTP expression may be helpful for diagnosis; and moreover, hepatic MTP activator may be a possible therapeutic agent for the treatment of NASH. Keywords:: non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver (NAFL), very-low-density lipoprotein (VLDL) synthesis, microsomal triglyceride transfer protein (MTP), potential drug target, liver disease