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

• Published in: eLife 2021-01, Vol.10
• Main Authors: Dai, Jian, Li, Ying, Kametani, Fuyuki, Cui, Xiaoran, Igarashi, Yuichi, Huo, Jia, Miyahara, Hiroki, Mori, Masayuki, Higuchi, Keiichi
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amyloid; Amyloidosis; Amyloidosis - genetics; Animals; Apolipoprotein A; Apolipoprotein A-II; Apolipoprotein A-II - metabolism; Biochemistry and Chemical Biology; Body fat; Curcumin; Curcumin - pharmacology; Dietary supplements; Enzymes; Fatty acids; Female; Food; Gene expression; High density lipoprotein; Homeostasis; Lipid metabolism; Liver; Metabolism; Mice; Nucleotide sequence; peroxisome; Peroxisome proliferator-activated receptors; Peroxisomes - drug effects; Peroxisomes - metabolism; Physiology; PPAR alpha - genetics; PPAR alpha - metabolism; PPARα; Proteins; Sequence analysis; Signal transduction; Signal Transduction - drug effects; Spleen
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.63538

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 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.