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

  • Published online on: December 14, 2016     https://doi.org/10.3892/ijmm.2016.2831
  • Pages: 407-414
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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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February-2017
Volume 39 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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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