Apolipoprotein A-1 accelerated liver regeneration through regulating autophagy via AMPK-ULK1 pathway

Background & aims: Apolipoprotein A-1 (ApoA-1), the main apolipoprotein of high-density lipoprotein, has been well studied in the area of lipid metabolism and cardiovascular diseases. In this project, we intended to clarify the function and mechanism of ApoA-1 in liver regeneration.

Methods: 70% of partial hepatectomy was applied in male ApoA-1 knockout mice and wild-type mice to investigate the effects of ApoA-1 on liver regeneration. D-4F (ApoA-1 mimetic peptide), Autophagy activator and AMPK Activator were used to explore the mechanism of ApoA-1 on liver regeneration.

Results: We demonstrated that ApoA-1 levels were highly expressed during the early stage of liver regeneration. ApoA-1 deficiency greatly impaired liver regeneration after hepatectomy. Meanwhile, we found that ApoA-1 deficiency inhibited Autophagy during liver regeneration. The activation of Autophagy protected against ApoA-1 deficiency in inhibiting liver regeneration. Furthermore, ApoA-1 deficiency impaired Autophagy through AMPK-ULK1 pathway, and AMPK activation significantly improved liver regeneration. The administration of D-4F could accelerated liver regeneration after hepatectomy.

Conclusions: These findings suggested that ApoA-1 played an essential role in liver regeneration through promoting Autophagy in hepatocytes via AMPK-ULK1 pathway. Our findings enriched the understanding of the underlying mechanism of liver regeneration and provided a potential therapeutic strategy for liver injury.

AMPK pathway; ApoA-1; Autophagy; Liver regeneration.