title: Interstrain differences in susceptibility to non-alcoholic steatohepatitis.
abstract: OBJECTIVE
  The pathophysiological mechanisms leading to the development of non-alcoholic steatohepatitis (NASH) remain unclear. There are differences in the susceptibility to NASH between the different species and sexes. The investigation of the precise mechanism of interstrain differences may provide new means by which the pathophysiological mechanisms of NASH may be understood.
  
  
  METHODS
  C57BL/6N and C3H/HeN mice were administered a methionine- and choline-deficient (MCD) diet to establish a dietary model of NASH.
  
  
  RESULTS
  An elevation of the serum alanine aminotransferase and increased infiltration of inflammatory cells were predominant in C57BL/6N mice at 8 weeks. The increase in the steatosis and lipid contents in the liver was greater in C57BL/6N mice than in C3H/HeN mice. The indices of lipid peroxidation demonstrated by F2-isoprostanes or 8-hydroxy-2'-deoxyguanosine also increased in the livers of C57BL/6N mice. Furthermore, Sirius red staining revealed an increase in the degree of fibrosis in C57BL/6N mice given the MCD diet. As a result, the C57BL/6N strain had a higher susceptibility to NASH than the C3H/HeN mice. The carnitine palmitoyltransferase 1A (in beta-oxidation) mRNA and mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase 2 (in ketogenesis) mRNA were downregulated in the C57BL/6N mice in comparison with C3H/HeN mice. There were no differences in the expression of microsomal triglyceride transfer protein or sterol regulatory element binding protein 1 between the C57BL/6N and C3H/HeN mice.
  
  
  CONCLUSIONS
  There were interstrain differences in susceptibility to NASH observed in a rodent dietary model. Further evaluations of the precise molecular mechanism of this interstrain difference may provide some indications of the pathophysiological mechanisms of NASH in humans.
authors.affiliation: Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Satoru
authors.initials: S
authors.lastname: Kakizaki
authors.forename: Daichi
authors.initials: D
authors.lastname: Takizawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Ken
authors.initials: K
authors.lastname: Sato
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takagi
authors.forename: Masatomo
authors.initials: M
authors.lastname: Mori
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001835:Body Weight; D002796:Choline Deficiency / Q000150:complications*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D005234:Fatty Liver / Q000209:etiology* / Q000473:pathology; D015870:Gene Expression; D050356:Lipid Metabolism / Q000235:genetics; D015227:Lipid Peroxidation; D008099:Liver / Q000033:anatomy & histology / Q000378:metabolism / Q000473:pathology; D008103:Liver Cirrhosis / Q000235:genetics; D008297:Male; D008715:Methionine / Q000172:deficiency*; D051379:Mice; D008809:Mice, Inbred C3H / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology*; D008810:Mice, Inbred C57BL / Q000033:anatomy & histology / Q000378:metabolism / Q000502:physiology*; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D013045:Species Specificity
chemical_list: D012333:RNA, Messenger; D008715:Methionine; D000410:Alanine Transaminase