Apolipoprotein A-1 Accelerated Liver Regeneration Through Regulating Autophagy Via AMPK-ULK1 Pathway.

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 clarify the function and mechanism of ApoA-1 in liver regeneration. Seventy percent 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. 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. These findings suggested that ApoA-1 played an essential role in liver regeneration through promoting autophagy in hepatocytes via AMPK-ULK1 pathway. Our findings enrich the understanding of the underlying mechanism of liver regeneration and provide a potential therapeutic strategy for liver injury. Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Zi Yi Wang, Rui Xiang Chen, Ji Fei Wang, Shuo Chen Liu, Xiao Xu, Tao Zhou, Yan An Lan Chen, Yao Dong Zhang, Xiang Cheng Li, Chang Xian Li. Apolipoprotein A-1 Accelerated Liver Regeneration Through Regulating Autophagy Via AMPK-ULK1 Pathway. Cellular and molecular gastroenterology and hepatology. 2024;17(4):539-551

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PMID: 38122985

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