Effect and mechanism of fisetin against the development of metabolic dysfunction-associated fatty liver disease

Figures

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  Fig. 1. Effects of fisetin and HFD on fasting blood glucose and glucose tolerance in mice. (A) Fasting blood glucose (n = 8). (B) Glucose tolerance test (n = 4). (C) Area under the curve (AUC) (n = 4). Data are presented as the means ± SEM. #P < 0.05, ##P < 0.01 versus CON group; *P < 0.05, **P < 0.05 versus HFD group.

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  Fig. 2. Effects of fisetin on serum lipids, AST and ALT, and SOD in mice fed high-fat diet. (A) Serum TG level (n = 8). (B) Serum TC level (n = 8). (C) Serum LDL-C level (n = 8). (D) Serum HDL-C level (n = 8). (E) Serum ALT level (n = 4). (F) Serum AST level (n = 4). (G) Serum SOD level (n = 4). Data are presented as the means ± SEM. #P < 0.05, ##P < 0.01 versus CON group;*P < 0.05,**P < 0.05 versus HFD group.

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  Fig. 3. Effects of fisetin on liver lipids, AST and ALT in HFD-fed mice fed. (A) Liver TG level (n = 8). (B) Liver TC level (n = 8). (C) Liver ALT level (n = 4). (D) Liver AST level (n = 4). (E) H&E staining of liver sections. (F) Oil Red O staining of liver sections. (G) PAS staining of liver sections. Data are presented as the means ± SEM. #P < 0.05, ##P < 0.01 versus CON group;*P < 0.05,**P < 0.05 versus HFD group.

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  Fig. 4. Effects of fisetin on liver gene expression profile in high-fat diet-fed mice. (A) Volcano plot visualizing the fold change of DEGs between the HFD and CON and between Fisetin and HFD mice. (B) Hierarchical clustering of DEGs. (C) GO enrichment analysis of DEGs in three GO categories including biological processes (BP), molecular functions (MF) and cellular components (CC). (D) KEGG enrichment analysis of DEGs. (E) Comparation of Log2FC values of six DEGs determined by RT-qPCR and RNA-Seq (n = 3). (F) The relative mRNA expression levels of Glut4, G6PC, PHGDH, GPx3, NQO1, IL-1β, and Cxcl10 (n = 4). Data are presented as the means ± SEM. #P < 0.05, ##P < 0.01 versus CON group;*P < 0.05,**P < 0.05 versus HFD group.

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  Fig. 5. Effects of fisetin on cell viability, lipid content and oxidative stress in OA-treated HepG2 cells. (A) Cell viability. (B) Intracellular TG. (C) Intracellular lipid content. (D) SOD contents in cell culture medium. (E) Intracellular GSH. (F) Intracellular ROS. (G) NO contents in cell culture medium. Data are presented as the means ± SEM (n = 3). #P < 0.05, ##P < 0.01 versus CON group; *P < 0.05,**P < 0.05 versus MOD group.

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  Fig. 6. Effects of fisetin on the expression of GSK-3β/Nrf2/HO-1 signaling pathway and PEPCK and G6PC in OA-treated induced HepG2 cells. (A) The relative expression levels of NRF2, HO-1, NQO1, PEPCK and G6PC mRNA s(n = 3–4). (B) Representative Western blots showing protein expressions of p-GSK3β, Nrf2, HO-1 and NQO1. (C) Ratio of p-GSK-3β/t-GSK-3β, Nrf2/β-actin, HO-1/β-actin, NQO1/β-actin (n = 3–4). (D) Ratios of PEPCK/β-actin and G6PC/β-actin (n = 3–4). (E) Representative Western blots showing protein expressions of PEPCK and G6PC. (F) Molecular docking of fisetin with the GSK-3β, HO-1, NQO1 and PEPCK proteins. Data are presented as the means ± SEM. #p < 0.05, ##p < 0.01 versus CON group;*p < 0.05, **p < 0.05 versus MOD group.