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Article

Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate non-alcoholic steatohepatitis via the suppression of oxidative stress and the upregulation of AMPK/ACC in high-fat diet-fed mice

  • Authors:
    • Takumi Kawaguchi
    • Takato Ueno
    • Yoichi Nogata
    • Masako Hayakawa
    • Hironori Koga
    • Takuji Torimura
  • View Affiliations / Copyright

    Affiliations: Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan, Asakura Medical Association Hospital, Asakura, Japan, NARO Western Region Agricultural Research Center, Kagawa, Japan, Liver Cancer Division, Research Center for Innovative Cancer Therapy, Kurume University, Kurume, Japan
  • Pages: 407-414
    |
    Published online on: December 14, 2016
       https://doi.org/10.3892/ijmm.2016.2831
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Abstract

Whole-wheat intake is known to reduce the risk of metabolic syndrome. However, the active component remains unclear. Recently, we identified bioactive peptides [leucine-arginine-proline (LRP) and leucine-glutamine‑proline (LQP)] from wheat bran autolytic hydrolysate. The present study aimed to investigate the effects of LRP and LQP on non-alcoholic steatohepatitis (NASH) in a mouse model. We also evaluated the effects of these peptides on oxidative stress and on the AMP-activated protein kinase (AMPK) signaling pathway, two major pathogenic factors of NASH. Seven‑week-old male C57BL/6 mice were fed a high-fat diet for 10 weeks and administered water supplemented with 0.05% LRP, 0.20% LRP, 0.05% LQP, or 0.20% LQP (each n=5) or distilled water (control; n=5) ad libitum. Oxidative stress was evaluated by measuring the serum levels of diacron reactive oxygen metabolite (d-ROM) and biological antioxidant potential (BAP). Hepatic expression of phosphorylated AMPK and phosphorylated acetyl-CoA carboxylase (ACC) were evaluated by immunoblotting. The result showed that non‑alcoholic fatty liver disease activity score was significantly decreased in all types of treatment. Serum d-ROM levels were significantly decreased in the 0.20% LRP group, but not in the 0.05% LRP, 0.05% LQP, and 0.20% LQP groups. Serum BAP levels were significantly increased in the 0.05% LRP and 0.20% LRP groups, but not in the 0.05% LQP and 0.20% LQP groups. Immunoblotting analysis revealed that the expression of phospho-AMPK was increased whereas that of phospho-ACC was decreased in the 0.20% LQP group. In conclusion, we demonstrated that both LRP and LQP alleviated the severity of NASH in a high-fat diet-induced NASH mouse model. In addition, we showed that LRP and LQP modulated oxidative stress and upregulated AMPK/ACC, respectively. Thus, LRP and LQP may constitute clinically applicable therapeutic agents for NASH.
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Copy and paste a formatted citation
Spandidos Publications style
Kawaguchi T, Ueno T, Nogata Y, Hayakawa M, Koga H and Torimura T: Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate non-alcoholic steatohepatitis via the suppression of oxidative stress and the upregulation of AMPK/ACC in high-fat diet-fed mice. Int J Mol Med 39: 407-414, 2017.
APA
Kawaguchi, T., Ueno, T., Nogata, Y., Hayakawa, M., Koga, H., & Torimura, T. (2017). Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate non-alcoholic steatohepatitis via the suppression of oxidative stress and the upregulation of AMPK/ACC in high-fat diet-fed mice. International Journal of Molecular Medicine, 39, 407-414. https://doi.org/10.3892/ijmm.2016.2831
MLA
Kawaguchi, T., Ueno, T., Nogata, Y., Hayakawa, M., Koga, H., Torimura, T."Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate non-alcoholic steatohepatitis via the suppression of oxidative stress and the upregulation of AMPK/ACC in high-fat diet-fed mice". International Journal of Molecular Medicine 39.2 (2017): 407-414.
Chicago
Kawaguchi, T., Ueno, T., Nogata, Y., Hayakawa, M., Koga, H., Torimura, T."Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate non-alcoholic steatohepatitis via the suppression of oxidative stress and the upregulation of AMPK/ACC in high-fat diet-fed mice". International Journal of Molecular Medicine 39, no. 2 (2017): 407-414. https://doi.org/10.3892/ijmm.2016.2831
Copy and paste a formatted citation
x
Spandidos Publications style
Kawaguchi T, Ueno T, Nogata Y, Hayakawa M, Koga H and Torimura T: Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate non-alcoholic steatohepatitis via the suppression of oxidative stress and the upregulation of AMPK/ACC in high-fat diet-fed mice. Int J Mol Med 39: 407-414, 2017.
APA
Kawaguchi, T., Ueno, T., Nogata, Y., Hayakawa, M., Koga, H., & Torimura, T. (2017). Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate non-alcoholic steatohepatitis via the suppression of oxidative stress and the upregulation of AMPK/ACC in high-fat diet-fed mice. International Journal of Molecular Medicine, 39, 407-414. https://doi.org/10.3892/ijmm.2016.2831
MLA
Kawaguchi, T., Ueno, T., Nogata, Y., Hayakawa, M., Koga, H., Torimura, T."Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate non-alcoholic steatohepatitis via the suppression of oxidative stress and the upregulation of AMPK/ACC in high-fat diet-fed mice". International Journal of Molecular Medicine 39.2 (2017): 407-414.
Chicago
Kawaguchi, T., Ueno, T., Nogata, Y., Hayakawa, M., Koga, H., Torimura, T."Wheat-bran autolytic peptides containing a branched-chain amino acid attenuate non-alcoholic steatohepatitis via the suppression of oxidative stress and the upregulation of AMPK/ACC in high-fat diet-fed mice". International Journal of Molecular Medicine 39, no. 2 (2017): 407-414. https://doi.org/10.3892/ijmm.2016.2831
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