title: [Mechanism Analysis and Prevention of Pathogenesis of Nonalcoholic Steatohepatitis].
abstract: Nonalcoholic fatty liver disease (NAFLD) is a common disease in humans having a broad spectrum of liver histology from simple fatty liver to mixed inflammatory cell infiltration and fibrosis (nonalcoholic steatohepatitis, NASH), which is a more severe and progressing form. NASH/NAFLD is significantly associated with lifestyle such as diet and exercise, obesity, insulin resistance, type 2 diabetes, dyslipidemia and hypertension. Age and gender are also associated with the development. On the other hand, NAFLD has been found in a high percentage of nonobese individuals in the Asia-Pacific area. Some characteristic animal models of NAFLD/NASH have been developed to clarify the pathogenesis of human NAFLD/NASH. We have recently developed a novel NASH rat model (stroke-prone spontaneously hypertensive rats, SHRSP5/Dmcr), which showed hepatic steatosis and inflammation at 2 weeks, ballooning, macrovesicular steatosis and fibrosis at 8 weeks, and bridging fibrosis at 14 weeks by feeding of high-fat and -cholesterol (HFC) diet alone. This animal model does not have obesity, insulin resistance or diabetes. Therefore, this may be an excellent animal model of human NASH/NAFLD without obesity and diabetes. Sex and strain differences observed in fibrogenesis by the HFC diet in SHRSP5/Dmcr may be associated with the sensitivity to detoxification enzymes in the liver, because the levels of UGP-glucuronosyltransferase and sulfotransferase and their regulating nuclear receptors only decreased in male SHRSP5/Dmcr rats, but not in female and SHRSP rats. This suggests the importance of phase II reactions of drug-metabolizing enzymes in NASH progression. Importantly, SHRSP5/Dmcr rats are spontaneously hypertensive; therefore, when we use the original strain Wistar Kyoto, which has normal blood pressure, the involvement of blood pressure in the development of human NASH/NAFLD may also be clarified.
authors.affiliation: College of Life and Health Sciences, Chubu University.
authors.forename: Tamie
authors.initials: T
authors.lastname: Nakajima
authors.forename: Hisao
authors.initials: H
authors.lastname: Naito
mesh_terms: D017677:Age Distribution; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D059305:Diet, High-Fat / Q000009:adverse effects; D004195:Disease Models, Animal; D050171:Dyslipidemias / Q000150:complications; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications; D007333:Insulin Resistance; D008019:Life Style; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications; D065626:Non-alcoholic Fatty Liver Disease / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control*; D009765:Obesity / Q000150:complications; D018384:Oxidative Stress; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012307:Risk Factors; D017678:Sex Distribution