title: Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr.
abstract: OBJECTIVE
  Patients with nonalcoholic fatty liver disease are increasing worldwide, and preventive measures are an urgent need and primary concern today.
  
  
  OBJECTIVE
  This study aimed to develop and clarify the usefulness of the SHRSP5/Dmcr rat, derived from a stroke-prone spontaneously hypertensive rat, as a novel animal model for time-course analysis of steatohepatitis and the severe fibrosis progression often observed in the disease.
  
  
  METHODS
  Ten-week-old male SHRSP5/Dmcr rats were divided into six groups: half were fed a high-fat and high-cholesterol-containing diet (HFC diet), and the others the control, stroke-prone (SP) diet for 2, 8, and 14 weeks.
  
  
  RESULTS
  The HFC diet significantly increased serum transaminase and gamma glutamyl transpeptidase activities, tumor necrosis factor alpha levels, and serum and hepatic total cholesterol levels over time. In contrast, this diet decreased serum albumin, glucose, and adiponectin levels throughout or the later stage of the feeding period, but did not influence serum insulin levels. Histopathologically, the HFC diet increased microvesicular steatosis, and focal or spotty necrosis with lymphocyte infiltrations were observed in the liver at 2 weeks, macrovesicular steatosis, ballooned hepatocytes with Mallory-Denk body formation in some, and multilobular necrosis and fibrosis at 8 weeks. Interestingly, this fibrosis formed a honeycomb network at 14 weeks. These changes are very similar to those observed in patients with non-alcoholic steatohepatitis.
  
  
  CONCLUSIONS
  SHRSP5/Dmcr rats appear to be a useful model for analyzing the time-dependent changes of HFC diet-induced steatohepatitis and fibrosis progression.
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kitamori
authors.forename: Hisao
authors.initials: H
authors.lastname: Naito
authors.forename: Hazuki
authors.initials: H
authors.lastname: Tamada
authors.forename: Miya
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Daisuke
authors.initials: D
authors.lastname: Miyazawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Yasui
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Sonoda
authors.forename: Satoru
authors.initials: S
authors.lastname: Tsuchikura
authors.forename: Naomi
authors.initials: N
authors.lastname: Yasui
authors.forename: Katsumi
authors.initials: K
authors.lastname: Ikeda
authors.forename: Takashi
authors.initials: T
authors.lastname: Moriya
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yamori
authors.forename: Tamie
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D052242:Adiponectin / Q000097:blood; D000418:Albumins / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects*; D004195:Disease Models, Animal; D018450:Disease Progression; D005234:Fatty Liver / Q000097:blood / Q000209:etiology* / Q000473:pathology; D007328:Insulin / Q000097:blood; D008099:Liver / Q000473:pathology; D008103:Liver Cirrhosis / Q000097:blood / Q000209:etiology* / Q000473:pathology; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR / Q000097:blood / Q000502:physiology; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015430:Weight Gain; D005723:gamma-Glutamyltransferase / Q000097:blood
chemical_list: D052242:Adiponectin; D000418:Albumins; D015415:Biomarkers; D001786:Blood Glucose; D002791:Cholesterol, Dietary; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D002784:Cholesterol; D005723:gamma-Glutamyltransferase; D000637:Transaminases