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

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

Research output: Contribution to journalArticle

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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 highcholesterol- 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.

Original languageEnglish
Pages (from-to)173-182
Number of pages10
JournalEnvironmental Health and Preventive Medicine
Volume17
Issue number3
DOIs
Publication statusPublished - 01-05-2012

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High Fat Diet
Fatty Liver
Fibrosis
Cholesterol
Diet
Fats
Necrosis
Mallory Bodies
Serum
Stroke
gamma-Glutamyltransferase
Liver
Adiponectin
Inbred SHR Rats
Transaminases
Serum Albumin
Hepatocytes
Animal Models
Tumor Necrosis Factor-alpha
Lymphocytes

All Science Journal Classification (ASJC) codes

  • Public Health, Environmental and Occupational Health

Cite this

Kitamori, Kazuya ; Naito, Hisao ; Tamada, Hazuki ; Kobayashi, Miya ; Miyazawa, Daisuke ; Yasui, Yuko ; Sonoda, Kunihiro ; Tsuchikura, Satoru ; Yasui, Naomi ; Ikeda, Katsumi ; Moriya, Takashi ; Yamori, Yukio ; Nakajima, Tamie. / Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr. In: Environmental Health and Preventive Medicine. 2012 ; Vol. 17, No. 3. pp. 173-182.
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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 highcholesterol- 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.",
author = "Kazuya Kitamori and Hisao Naito and Hazuki Tamada and Miya Kobayashi and Daisuke Miyazawa and Yuko Yasui and Kunihiro Sonoda and Satoru Tsuchikura and Naomi Yasui and Katsumi Ikeda and Takashi Moriya and Yukio Yamori and Tamie Nakajima",
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Kitamori, K, Naito, H, Tamada, H, Kobayashi, M, Miyazawa, D, Yasui, Y, Sonoda, K, Tsuchikura, S, Yasui, N, Ikeda, K, Moriya, T, Yamori, Y & Nakajima, T 2012, 'Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr', Environmental Health and Preventive Medicine, vol. 17, no. 3, pp. 173-182. https://doi.org/10.1007/s12199-011-0235-9

Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr. / Kitamori, Kazuya; Naito, Hisao; Tamada, Hazuki; Kobayashi, Miya; Miyazawa, Daisuke; Yasui, Yuko; Sonoda, Kunihiro; Tsuchikura, Satoru; Yasui, Naomi; Ikeda, Katsumi; Moriya, Takashi; Yamori, Yukio; Nakajima, Tamie.

In: Environmental Health and Preventive Medicine, Vol. 17, No. 3, 01.05.2012, p. 173-182.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Development of novel rat model for high-fat and high-cholesterol diet-induced steatohepatitis and severe fibrosis progression in SHRSP5/Dmcr

AU - Kitamori, Kazuya

AU - Naito, Hisao

AU - Tamada, Hazuki

AU - Kobayashi, Miya

AU - Miyazawa, Daisuke

AU - Yasui, Yuko

AU - Sonoda, Kunihiro

AU - Tsuchikura, Satoru

AU - Yasui, Naomi

AU - Ikeda, Katsumi

AU - Moriya, Takashi

AU - Yamori, Yukio

AU - Nakajima, Tamie

PY - 2012/5/1

Y1 - 2012/5/1

N2 - 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 highcholesterol- 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.

AB - 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 highcholesterol- 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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U2 - 10.1007/s12199-011-0235-9

DO - 10.1007/s12199-011-0235-9

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