TY - JOUR
T1 - Mechanism Analysis and Prevention of Pathogenesis of Nonalcoholic Steatohepatitis
AU - Nakajima, Tamie
AU - Naito, Hisao
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
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U2 - 10.1265/jjh.70.197
DO - 10.1265/jjh.70.197
M3 - Review article
C2 - 26411937
AN - SCOPUS:84973496037
SN - 0021-5082
VL - 70
SP - 197
EP - 204
JO - Nihon eiseigaku zasshi. Japanese journal of hygiene
JF - Nihon eiseigaku zasshi. Japanese journal of hygiene
IS - 3
ER -