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Environmental Health and Preventive Medicine

Published in:

01-05-2012 | Regular Article

Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr

Authors: Kazuya Kitamori, Hisao Naito, Hazuki Tamada, Miya Kobayashi, Daisuke Miyazawa, Yuko Yasui, Kunihiro Sonoda, Satoru Tsuchikura, Naomi Yasui, Katsumi Ikeda, Takashi Moriya, Yukio Yamori, Tamie Nakajima

Published in: Environmental Health and Preventive Medicine | Issue 3/2012

Abstract

Objectives

Patients with nonalcoholic fatty liver disease are increasing worldwide, and preventive measures are an urgent need and primary concern today.

Aim

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.

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Title: Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr
Authors: Kazuya Kitamori
Hisao Naito
Hazuki Tamada
Miya Kobayashi
Daisuke Miyazawa
Yuko Yasui
Kunihiro Sonoda
Satoru Tsuchikura
Naomi Yasui
Katsumi Ikeda
Takashi Moriya
Yukio Yamori
Tamie Nakajima
Publication date: 01-05-2012
Publisher: Springer Japan
Published in: Environmental Health and Preventive Medicine / Issue 3/2012
Print ISSN: 1342-078X
Electronic ISSN: 1347-4715
DOI: https://doi.org/10.1007/s12199-011-0235-9

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr

Abstract

Objectives

Aim

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Aim

Methods

Results

Conclusions

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