Apolipoprotein A-1 accelerated liver regeneration through regulating autophagy via AMPK-ULK1 pathway
- Cell Mol Gastroenterol Hepatol. 2023 Dec 18:S2352-345X(23)00217-5. doi: 10.1016/j.jcmgh.2023.12.004.
- 1. Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China.
- 2. Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China. Electronic address: [email protected].
- 3. Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University; Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, Nanjing, China. Electronic address: [email protected].
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.