Curcumin promotes AApoAII amyloidosis and peroxisome proliferation in mice by activating the PPARα signaling pathway

  1. Jian Dai  Is a corresponding author
  2. Ying Li
  3. Fuyuki Kametani
  4. Xiaoran Cui
  5. Yuichi Igarashi
  6. Jia Huo
  7. Hiroki Miyahara
  8. Masayuki Mori
  9. Keiichi Higuchi
  1. Shinshu University, Japan
  2. Tokyo Metropolitan Institute of Medical Science, Japan
  3. Shinshu University Graduate School of Medicine, Japan
  4. Third Hospital of Hebei Medical University, China

Abstract

Curcumin is a polyphenol compound that exhibits multiple physiological activities. To elucidate the mechanisms by which curcumin affects systemic amyloidosis, we investigated amyloid deposition and molecular changes in a mouse model of amyloid apolipoprotein A-II (AApoAII) amyloidosis, in which mice were fed a curcumin-supplemented diet. Curcumin supplementation for 12 weeks significantly increased AApoAII amyloid deposition relative to controls, especially in the liver and spleen. Liver weights and plasma ApoA-II and high-density lipoprotein concentrations were significantly elevated in curcumin-supplemented groups. RNA-sequence analysis revealed that curcumin intake affected hepatic lipid metabolism via the peroxisome proliferator-activated receptor (PPAR) pathway, especially PPARα activation, resulting in increased Apoa2 mRNA expression. The increase in liver weights was due to activation of PPARα and peroxisome proliferation. Taken together, these results demonstrate that curcumin is a PPARα activator and may affect expression levels of proteins involved in amyloid deposition to influence amyloidosis and metabolism in a complex manner.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Jian Dai

    Aging Biology, Shinshu University, Matsumoto, Japan
    For correspondence
    daijian3@shinshu-u.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8097-6756
  2. Ying Li

    Aging Biology, Shinshu University, Matsumoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Fuyuki Kametani

    Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Xiaoran Cui

    Shinshu University Graduate School of Medicine, Matsumoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Yuichi Igarashi

    Shinshu University Graduate School of Medicine, Matsumoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Jia Huo

    Third Hospital of Hebei Medical University, Shijiazhuang, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Hiroki Miyahara

    Aging Biology, Shinshu University, Matsumoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
  8. Masayuki Mori

    Aging Biology, Shinshu University, Matsumoto, Japan
    Competing interests
    The authors declare that no competing interests exist.
  9. Keiichi Higuchi

    Aging Biology, Shinshu University, Matsumoto, Japan
    Competing interests
    The authors declare that no competing interests exist.

Funding

Ministry of Education, Culture, Sports, Science and Technology (17H04063)

  • Jian Dai

Ministry of Education, Culture, Sports, Science and Technology (26670152)

  • Jian Dai

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were approved by the Committee for Animal Experiments of Shinshu University (Approval No. 280086). Mice were sacrificed by cardiac puncture under deep sevoflurane anesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Rudolph E Tanzi, Harvard University, United States

Publication history

  1. Received: September 28, 2020
  2. Accepted: January 10, 2021
  3. Accepted Manuscript published: January 26, 2021 (version 1)
  4. Version of Record published: February 12, 2021 (version 2)

Copyright

© 2021, Dai et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jian Dai
  2. Ying Li
  3. Fuyuki Kametani
  4. Xiaoran Cui
  5. Yuichi Igarashi
  6. Jia Huo
  7. Hiroki Miyahara
  8. Masayuki Mori
  9. Keiichi Higuchi
(2021)
Curcumin promotes AApoAII amyloidosis and peroxisome proliferation in mice by activating the PPARα signaling pathway
eLife 10:e63538.
https://doi.org/10.7554/eLife.63538

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