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