Curcumin promotes AApoAII amyloidosis and peroxisome proliferation in mice by activating the PPARα signaling pathway
- Department of Neuro-health Innovation, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, Japan
- Department of Pathology, the Xiehe Hospital of Tangshan, China
- Aging Biology, Department of Biomedical Engineering, Graduate School of Medicine, Science and Technology Shinshu University, Japan
- Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Japan
- Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, Japan
- Department of Orthopedic Surgery, the Third Hospital of Hebei Medical University, China
- Department of Aging Biology, Shinshu University School of Medicine, Japan
Figures
Figure 1 with 7 supplements
Degree of AApoAII amyloid deposition and liver weights.
(a) Amyloid index (AI) in the 8-week group. (b) Representative Congo red and IHC images of AApoAII amyloid deposition in the 8-week group. Amyloid deposits (red arrows) were identified by green …
Figure 1—figure supplement 1
Experimental design.
Eight-week-old female R1.P1-Apoa2c mice were divided into four groups: control (Con) group, curcumin (Cur) group, amyloid and no-treatment (A-NT) group, and amyloid and curcumin (A-Cur) group. The …
Figure 1—figure supplement 2
Weekly body weight and food intake measurements.
(a) Body weight and (b) food intake in the 8-week group. Each column and bar represent the mean ± S.D. (N = 3–5). (c) Body weight and (d) food intake in the 12-week group. Data are represented in …
Figure 1—figure supplement 3
Amyloid score in various organs.
(a) Amyloid deposition in the liver and spleen is increased by supplementation with curcumin for 8 weeks. (b) Amyloid score in other organs (heart, stomach, intestine, tongue, skin, lung, and …
Figure 1—figure supplement 4
Hepatocyte hypertrophy in curcumin intake groups.
(a) Representative HE stained image of hepatocytes. Large nuclei (black arrows) were identified in curcumin intake groups. Each scale bar indicates 20 μm. (b) Average hepatocyte size in each group. …
Figure 1—figure supplement 5
No differences in AST and ALT plasma concentrations after curcumin intake.
AST and ALT plasma levels were detected to evaluate hepatocyte injury. (a) AST and ALT concentrations in the 8-week group. (b) AST and ALT plasma concentrations in the 12-week group. Data are mean ± …
Figure 1—figure supplement 6
Inflammation-related gene expression in the liver in the 12-week group.
Representative genes related to inflammation were measured by real-time qPCR. Results show that curcumin does not affect the expression of inflammatory genes, but Tnfα was increased in the A-Cur …
Figure 1—figure supplement 7
Degree of AApoAII amyloid deposition and liver weights were significantly increased after supplementation with low dose curcumin diet (0.5% w/w).
(a) Amyloid index (AI) in the 12-week group supplemented with 0.5% curcumin diet. Each dot represents an individual mouse. (b) Ratio of liver weight/body weight in the 12-week group. Data are mean ± …
Figure 2 with 1 supplement
Curcumin elevated ApoA-II levels and affected lipid metabolism in mice after 12 weeks.
(a–c) Plasma concentrations of ApoA-II, ApoA-I, and ApoE were determined by densitometry of Western immunoblot after SDS-PAGE. Representative results of western blot are shown above the figures. …
Figure 2—figure supplement 1
ApoA-II, ApoA-I, and ApoE plasma levels after supplementation with 2% w/w curcumin diet for 8 weeks.
(a–c) Plasma levels of ApoA-II, ApoA-I, and ApoE proteins were determined by western immunoblot. There were no obvious changes in ApoA-II and ApoA-I plasma concentrations; the concentration of ApoE …
Figure 3 with 1 supplement
RNA sequence analysis showed that curcumin regulates many lipid metabolism-related genes via the peroxisome proliferator-activated receptor (PPAR) signaling pathway.
(a) The Venn diagram shows that 75 genes are changed in the liver by supplementation with curcumin for 12 weeks. (b) Enrichment pathway analysis based on the KEGG database. (c and d) The Volcano …
-
Figure 3—source data 1
Cur vs Con.DEG.
- https://cdn.elifesciences.org/articles/63538/elife-63538-fig3-data1-v2.xls
-
Figure 3—source data 2
ACur vs ANT.DEGs.
- https://cdn.elifesciences.org/articles/63538/elife-63538-fig3-data2-v2.xls
-
Figure 3—source data 3
the list of 75 DEGs.
- https://cdn.elifesciences.org/articles/63538/elife-63538-fig3-data3-v2.xlsx
-
Figure 3—source data 4
CurvsCon_all.DEG_KEGG_pathway_enrichment.
- https://cdn.elifesciences.org/articles/63538/elife-63538-fig3-data4-v2.xls
-
Figure 3—source data 5
ACurvsANT_all.DEG_KEGG_pathway_enrichment.
- https://cdn.elifesciences.org/articles/63538/elife-63538-fig3-data5-v2.xls
Figure 3—figure supplement 1
mRNA expression of Pparγ in the liver.
Pparγ expression in the liver is upregulated in curcumin intake groups. Histograms show fold changes relative to the Con group. Data are mean ± SD. The Tukey–Kramer method was used for multiple …
Figure 4
PPARα levels in the liver are increased and show more intranuclear localization in curcumin-supplemented mice.
(a) Immunofluorescence results of PPARa showed obvious intranuclear signal accumulation and extranuclear signal enhancement after curcumin ingestion. (b) Levels of PPARa proteins in the liver were …
Figure 5
Peroxisome and fatty acid oxidative enzymes are increased in the liver.
IHC (a) and western blot (b) results confirmed that catalase was significantly increased after curcumin supplementation. (c) The protein band near 75 kD of liver lysates exhibited different …
Figure 6
Schematic diagram of the effect of curcumin mediated by PPARa in mouse liver.
Curcumin regulates gene expression via PPARa activation and exhibits biological activities involved in amyloidosis, peroxisome proliferation, lipid metabolism, and hepatocyte hypertrophy.
Additional files
-
Supplementary file 1
Liver and body weight.
- https://cdn.elifesciences.org/articles/63538/elife-63538-supp1-v2.xlsx
-
Supplementary file 2
70KD-proteomics.
- https://cdn.elifesciences.org/articles/63538/elife-63538-supp2-v2.xlsx
-
Supplementary file 3
Primers.
- https://cdn.elifesciences.org/articles/63538/elife-63538-supp3-v2.docx
-
Transparent reporting form
- https://cdn.elifesciences.org/articles/63538/elife-63538-transrepform-v2.docx
