Exercise ameliorates nonalcoholic fatty liver disease by reducing the IGFBP5 to IGF1 ratio to activate AMPK pathway

Figures

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  Fig. 1. Exercise reduced HFD-induced liver weight, hepatic steatosis, inflammation, and fibrosis. The liver weight (A) decreased after 12 weeks of treadmill training. Hepatic histological analysis of steatosis, inflammation, ballooning, and NAFLD activity score (NAS) (B). Liver sections stained with H&E (×200) (C). Hepatic TC levels and TG levels (D). Hepatic lipid accumulation as determined by Oil Red O staining (×200) (E). Collagen content determined by counting Sirius Red positive areas in six randomly selected fields using Image Pro Plus 6.0 software and hepatic mRNA levels of Collagen I (F). Liver sections stained with Sirius Red (×200) (G). Serum ALT and AST levels (H). Results are presented as the mean ± SEM, n = 6 per group. * P < 0.05, ** P < 0.01, and *** P < 0.001.

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  Fig. 2. Exercise relieves HFD-induced insulin resistance. Fasting blood glucose (A), serum insulin levels (B) and the HOMA-IR index (C). Glucose tolerance test (GTT) (D) and insulin tolerance test (ITT) (E). Results are presented as the mean ± SEM, n = 6 per group. *** P < 0.001 (HFD vs. HFD + EXE).

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  Fig. 3. Exercise reduced HFD-induced serum IGFBP5/IGF1 ratio. All identified proteins were classified according to the top 20 gene ontology ratios sorted by enrichment degree [− log10 (p-value)] (A). Chord diagram of top 10 differentially expressed proteins among the LFD, HFD and HFD + EXE groups (red represents up-regulation, blue represents down-regulation) (B). Heat map of differentially expressed proteins among the LFD, HFD and HFD + EXE groups (red represents up-regulation, blue represents down-regulation) (C). EILSA results of serum IGFBP5, total IGF1 and free IGF1 levels (D). Results are presented as the mean ± SEM, n = 3 or 6 per group. ns P > 0.05 and ***P < 0.001.

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  Fig. 4. Exercise activated IRS1/Akt/AMPK pathway due to reduce serum IGFBP5/total IGF1 ratio. (A). Protein levels of IGFBP5, IGF1, IGF1R, IRS1, p-IRS1 (Ser307), p-IRS1 (Tyr612), Akt, p-Akt (Ser473), AMPKα and p-AMPKα (Thr183/172) in mouse livers were assayed by western blot. (B). Protein expression results are presented as the mean ± SEM, n = 6 per group. ns P > 0.05, ** P < 0.01 and ***P < 0.001.

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  Fig. 5. Exercise activated the effects of IGF1 by reducing the serum IGFBP5/IGF1 ratio, consequently triggering the IRS1/Akt/AMPK signaling pathway to ameliorate HFD-induced NAFLD.