The modulation of hepatic adenosine triphosphate and inflammation by eicosapentaenoic acid during severe fibrotic progression in the SHRSP5/Dmcr rat model

Xiaofang Jia, Hisao Naito, Husna Yetti, Hazuki Tamada, Kazuya Kitamori, Yumi Hayashi, Nozomi Yamagishi, Dong Wang, Yukie Yanagiba, Yuki Ito, Juncai Wang, Naoki Tanaka, Katsumi Ikeda, Yukio Yamori, Tamie Nakajima

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Aims: Eicosapentaenoic acid (EPA) can ameliorate certain liver lesions involved in non-alcoholic steatohepatitis (NASH). A previous study has found that stroke-prone spontaneously hypertensive 5/Dmcr (SHRSP5/Dmcr) rats fed a high fat-cholesterol (HFC) diet developed fibrotic steatohepatitis with histological similarities to NASH. This study evaluated the potential effects and mechanisms of action of EPA supplementation using this rodent model. Main methods: Male rats were randomly assigned to groups that were fed with either the stroke-prone (SP) diet or HFC diet with or without EPA for 2, 8 and 14 weeks, respectively. The liver histopathology, biochemical features, mRNA and protein levels, and nuclear factor-κB (NF-κB) DNA binding activity were determined. Key findings: The SP diet-fed rats presented normal livers. Conversely, the HFC diet-fed rats developed microvesicular/macrovesicular steatosis, inflammation, ballooning degeneration and severe fibrosis. At 2 weeks, the administration of EPA inhibited hepatic inflammatory recruitment by blocking the phosphorylation of inhibitor of κB-α (IκBα), which antagonizes the NF-κB activation pathway. The dietary supplementation of EPA for 8 weeks ameliorated hepatic triglyceride accumulation and macrovesicular steatosis by inhibiting the HFC diet-induced decrease in the protein levels of enzymes involved in fatty acid β-oxidation including carnitine palmitoyltransferase 1, very long chain acyl-CoA dehydrogenase and peroxisomal bifunctional protein. Although the administration of EPA elicited no histologically detectable effects on severe fibrosis at 14 weeks, it restored an HFC diet-induced decline in hepatic adenosine triphosphate (ATP) levels and suppressed ballooning degeneration, suggesting that EPA may inhibit HFC diet-induced ATP loss and cell death. Significance: Initial amelioration of the inflammation and steatosis in the rats after EPA supplementation indicates a possibility to treat steatohepatitis. Additionally, this study provides new insights into the roles of EPA in hepatic ATP depletion and subsequent hepatocellular injury during severe fibrosis.

Original languageEnglish
Pages (from-to)934-943
Number of pages10
JournalLife Sciences
Volume90
Issue number23-24
DOIs
Publication statusPublished - 14-06-2012

Fingerprint

Eicosapentaenoic Acid
Nutrition
Rats
Adenosine Triphosphate
Modulation
High Fat Diet
Inflammation
Liver
Fats
Cholesterol
Fatty Liver
Fibrosis
Stroke
Long-Chain Acyl-CoA Dehydrogenase
Diet
Carnitine O-Palmitoyltransferase
Phosphorylation
Proteins
Cell death
Nuclear Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Jia, Xiaofang ; Naito, Hisao ; Yetti, Husna ; Tamada, Hazuki ; Kitamori, Kazuya ; Hayashi, Yumi ; Yamagishi, Nozomi ; Wang, Dong ; Yanagiba, Yukie ; Ito, Yuki ; Wang, Juncai ; Tanaka, Naoki ; Ikeda, Katsumi ; Yamori, Yukio ; Nakajima, Tamie. / The modulation of hepatic adenosine triphosphate and inflammation by eicosapentaenoic acid during severe fibrotic progression in the SHRSP5/Dmcr rat model. In: Life Sciences. 2012 ; Vol. 90, No. 23-24. pp. 934-943.
@article{3d4739afb75a4cf0a5d3c2724aadfacb,
title = "The modulation of hepatic adenosine triphosphate and inflammation by eicosapentaenoic acid during severe fibrotic progression in the SHRSP5/Dmcr rat model",
abstract = "Aims: Eicosapentaenoic acid (EPA) can ameliorate certain liver lesions involved in non-alcoholic steatohepatitis (NASH). A previous study has found that stroke-prone spontaneously hypertensive 5/Dmcr (SHRSP5/Dmcr) rats fed a high fat-cholesterol (HFC) diet developed fibrotic steatohepatitis with histological similarities to NASH. This study evaluated the potential effects and mechanisms of action of EPA supplementation using this rodent model. Main methods: Male rats were randomly assigned to groups that were fed with either the stroke-prone (SP) diet or HFC diet with or without EPA for 2, 8 and 14 weeks, respectively. The liver histopathology, biochemical features, mRNA and protein levels, and nuclear factor-κB (NF-κB) DNA binding activity were determined. Key findings: The SP diet-fed rats presented normal livers. Conversely, the HFC diet-fed rats developed microvesicular/macrovesicular steatosis, inflammation, ballooning degeneration and severe fibrosis. At 2 weeks, the administration of EPA inhibited hepatic inflammatory recruitment by blocking the phosphorylation of inhibitor of κB-α (IκBα), which antagonizes the NF-κB activation pathway. The dietary supplementation of EPA for 8 weeks ameliorated hepatic triglyceride accumulation and macrovesicular steatosis by inhibiting the HFC diet-induced decrease in the protein levels of enzymes involved in fatty acid β-oxidation including carnitine palmitoyltransferase 1, very long chain acyl-CoA dehydrogenase and peroxisomal bifunctional protein. Although the administration of EPA elicited no histologically detectable effects on severe fibrosis at 14 weeks, it restored an HFC diet-induced decline in hepatic adenosine triphosphate (ATP) levels and suppressed ballooning degeneration, suggesting that EPA may inhibit HFC diet-induced ATP loss and cell death. Significance: Initial amelioration of the inflammation and steatosis in the rats after EPA supplementation indicates a possibility to treat steatohepatitis. Additionally, this study provides new insights into the roles of EPA in hepatic ATP depletion and subsequent hepatocellular injury during severe fibrosis.",
author = "Xiaofang Jia and Hisao Naito and Husna Yetti and Hazuki Tamada and Kazuya Kitamori and Yumi Hayashi and Nozomi Yamagishi and Dong Wang and Yukie Yanagiba and Yuki Ito and Juncai Wang and Naoki Tanaka and Katsumi Ikeda and Yukio Yamori and Tamie Nakajima",
year = "2012",
month = "6",
day = "14",
doi = "10.1016/j.lfs.2012.04.029",
language = "English",
volume = "90",
pages = "934--943",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "23-24",

}

Jia, X, Naito, H, Yetti, H, Tamada, H, Kitamori, K, Hayashi, Y, Yamagishi, N, Wang, D, Yanagiba, Y, Ito, Y, Wang, J, Tanaka, N, Ikeda, K, Yamori, Y & Nakajima, T 2012, 'The modulation of hepatic adenosine triphosphate and inflammation by eicosapentaenoic acid during severe fibrotic progression in the SHRSP5/Dmcr rat model', Life Sciences, vol. 90, no. 23-24, pp. 934-943. https://doi.org/10.1016/j.lfs.2012.04.029

The modulation of hepatic adenosine triphosphate and inflammation by eicosapentaenoic acid during severe fibrotic progression in the SHRSP5/Dmcr rat model. / Jia, Xiaofang; Naito, Hisao; Yetti, Husna; Tamada, Hazuki; Kitamori, Kazuya; Hayashi, Yumi; Yamagishi, Nozomi; Wang, Dong; Yanagiba, Yukie; Ito, Yuki; Wang, Juncai; Tanaka, Naoki; Ikeda, Katsumi; Yamori, Yukio; Nakajima, Tamie.

In: Life Sciences, Vol. 90, No. 23-24, 14.06.2012, p. 934-943.

Research output: Contribution to journalArticle

TY - JOUR

T1 - The modulation of hepatic adenosine triphosphate and inflammation by eicosapentaenoic acid during severe fibrotic progression in the SHRSP5/Dmcr rat model

AU - Jia, Xiaofang

AU - Naito, Hisao

AU - Yetti, Husna

AU - Tamada, Hazuki

AU - Kitamori, Kazuya

AU - Hayashi, Yumi

AU - Yamagishi, Nozomi

AU - Wang, Dong

AU - Yanagiba, Yukie

AU - Ito, Yuki

AU - Wang, Juncai

AU - Tanaka, Naoki

AU - Ikeda, Katsumi

AU - Yamori, Yukio

AU - Nakajima, Tamie

PY - 2012/6/14

Y1 - 2012/6/14

N2 - Aims: Eicosapentaenoic acid (EPA) can ameliorate certain liver lesions involved in non-alcoholic steatohepatitis (NASH). A previous study has found that stroke-prone spontaneously hypertensive 5/Dmcr (SHRSP5/Dmcr) rats fed a high fat-cholesterol (HFC) diet developed fibrotic steatohepatitis with histological similarities to NASH. This study evaluated the potential effects and mechanisms of action of EPA supplementation using this rodent model. Main methods: Male rats were randomly assigned to groups that were fed with either the stroke-prone (SP) diet or HFC diet with or without EPA for 2, 8 and 14 weeks, respectively. The liver histopathology, biochemical features, mRNA and protein levels, and nuclear factor-κB (NF-κB) DNA binding activity were determined. Key findings: The SP diet-fed rats presented normal livers. Conversely, the HFC diet-fed rats developed microvesicular/macrovesicular steatosis, inflammation, ballooning degeneration and severe fibrosis. At 2 weeks, the administration of EPA inhibited hepatic inflammatory recruitment by blocking the phosphorylation of inhibitor of κB-α (IκBα), which antagonizes the NF-κB activation pathway. The dietary supplementation of EPA for 8 weeks ameliorated hepatic triglyceride accumulation and macrovesicular steatosis by inhibiting the HFC diet-induced decrease in the protein levels of enzymes involved in fatty acid β-oxidation including carnitine palmitoyltransferase 1, very long chain acyl-CoA dehydrogenase and peroxisomal bifunctional protein. Although the administration of EPA elicited no histologically detectable effects on severe fibrosis at 14 weeks, it restored an HFC diet-induced decline in hepatic adenosine triphosphate (ATP) levels and suppressed ballooning degeneration, suggesting that EPA may inhibit HFC diet-induced ATP loss and cell death. Significance: Initial amelioration of the inflammation and steatosis in the rats after EPA supplementation indicates a possibility to treat steatohepatitis. Additionally, this study provides new insights into the roles of EPA in hepatic ATP depletion and subsequent hepatocellular injury during severe fibrosis.

AB - Aims: Eicosapentaenoic acid (EPA) can ameliorate certain liver lesions involved in non-alcoholic steatohepatitis (NASH). A previous study has found that stroke-prone spontaneously hypertensive 5/Dmcr (SHRSP5/Dmcr) rats fed a high fat-cholesterol (HFC) diet developed fibrotic steatohepatitis with histological similarities to NASH. This study evaluated the potential effects and mechanisms of action of EPA supplementation using this rodent model. Main methods: Male rats were randomly assigned to groups that were fed with either the stroke-prone (SP) diet or HFC diet with or without EPA for 2, 8 and 14 weeks, respectively. The liver histopathology, biochemical features, mRNA and protein levels, and nuclear factor-κB (NF-κB) DNA binding activity were determined. Key findings: The SP diet-fed rats presented normal livers. Conversely, the HFC diet-fed rats developed microvesicular/macrovesicular steatosis, inflammation, ballooning degeneration and severe fibrosis. At 2 weeks, the administration of EPA inhibited hepatic inflammatory recruitment by blocking the phosphorylation of inhibitor of κB-α (IκBα), which antagonizes the NF-κB activation pathway. The dietary supplementation of EPA for 8 weeks ameliorated hepatic triglyceride accumulation and macrovesicular steatosis by inhibiting the HFC diet-induced decrease in the protein levels of enzymes involved in fatty acid β-oxidation including carnitine palmitoyltransferase 1, very long chain acyl-CoA dehydrogenase and peroxisomal bifunctional protein. Although the administration of EPA elicited no histologically detectable effects on severe fibrosis at 14 weeks, it restored an HFC diet-induced decline in hepatic adenosine triphosphate (ATP) levels and suppressed ballooning degeneration, suggesting that EPA may inhibit HFC diet-induced ATP loss and cell death. Significance: Initial amelioration of the inflammation and steatosis in the rats after EPA supplementation indicates a possibility to treat steatohepatitis. Additionally, this study provides new insights into the roles of EPA in hepatic ATP depletion and subsequent hepatocellular injury during severe fibrosis.

UR - http://www.scopus.com/inward/record.url?scp=84862002562&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862002562&partnerID=8YFLogxK

U2 - 10.1016/j.lfs.2012.04.029

DO - 10.1016/j.lfs.2012.04.029

M3 - Article

C2 - 22569299

AN - SCOPUS:84862002562

VL - 90

SP - 934

EP - 943

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 23-24

ER -