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Article Open Access

Activation of AMPK pathway by low‑dose donafenib and atorvastatin combination improves high‑fat diet‑induced metabolic dysfunction‑associated steatotic liver disease

  • Authors:
    • Yaowei Bai
    • Kequan Chen
    • Jiacheng Liu
    • Yingliang Wang
    • Chaoyang Wang
    • Shuguang Ju
    • Chen Zhou
    • Wei Yao
    • Bin Xiong
    • Chuansheng Zheng
  • View Affiliations / Copyright

    Affiliations: Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430022, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China, Department of Interventional Radiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510120, P.R. China
    Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 51
    |
    Published online on: January 29, 2024
       https://doi.org/10.3892/mmr.2024.13175
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Abstract

Metabolic dysfunction‑associated steatotic liver disease (MASLD) is an increasingly significant global health burden for which there is currently no effective treatment. The present study aimed to explore the underlying mechanisms and investigate the effects of donafenib and atorvastatin in MASLD. The effects of donafenib and atorvastatin on the activity and lipid metabolism of HepG2 cells were analyzed in vitro. A rat model of MASLD was established induced by a high‑fat diet in vivo. H&E and Oil red O staining were used to observe the improvement in MASLD, western blotting analysis was used to detect the expression of proteins related to fat metabolism and immunofluorescence was used to detect reactive oxygen species (ROS) levels. In vitro, donafenib and atorvastatin inhibited lipid accumulation in HepG2 cells. In vivo, donafenib and atorvastatin activated the AMP‑activated protein kinase (AMPK) pathway, downregulated the expressions of proteins related to fatty acid synthesis (sterol regulatory element‑binding protein‑1, 3‑hydroxy‑3‑methylglutaryl‑CoA reductase and fatty acid synthase) and upregulated the expression of proteins related to fatty acid β‑oxidation (carnitine palmitoyl‑transferase 1C and acyl‑CoA oxidase). The levels of free fatty acids, cholesterol and triglycerides in the liver and serum decreased in all three treatment groups. Additionally, donafenib and atorvastatin reduced oxidative stress in the liver tissue and decreased ROS levels. Low‑dose donafenib combined with atorvastatin improved MASLD by regulating fatty acid metabolism and reducing oxidative stress through activation of the AMPK signaling pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Bai Y, Chen K, Liu J, Wang Y, Wang C, Ju S, Zhou C, Yao W, Xiong B, Zheng C, Zheng C, et al: Activation of AMPK pathway by low‑dose donafenib and atorvastatin combination improves high‑fat diet‑induced metabolic dysfunction‑associated steatotic liver disease. Mol Med Rep 29: 51, 2024.
APA
Bai, Y., Chen, K., Liu, J., Wang, Y., Wang, C., Ju, S. ... Zheng, C. (2024). Activation of AMPK pathway by low‑dose donafenib and atorvastatin combination improves high‑fat diet‑induced metabolic dysfunction‑associated steatotic liver disease. Molecular Medicine Reports, 29, 51. https://doi.org/10.3892/mmr.2024.13175
MLA
Bai, Y., Chen, K., Liu, J., Wang, Y., Wang, C., Ju, S., Zhou, C., Yao, W., Xiong, B., Zheng, C."Activation of AMPK pathway by low‑dose donafenib and atorvastatin combination improves high‑fat diet‑induced metabolic dysfunction‑associated steatotic liver disease". Molecular Medicine Reports 29.3 (2024): 51.
Chicago
Bai, Y., Chen, K., Liu, J., Wang, Y., Wang, C., Ju, S., Zhou, C., Yao, W., Xiong, B., Zheng, C."Activation of AMPK pathway by low‑dose donafenib and atorvastatin combination improves high‑fat diet‑induced metabolic dysfunction‑associated steatotic liver disease". Molecular Medicine Reports 29, no. 3 (2024): 51. https://doi.org/10.3892/mmr.2024.13175
Copy and paste a formatted citation
x
Spandidos Publications style
Bai Y, Chen K, Liu J, Wang Y, Wang C, Ju S, Zhou C, Yao W, Xiong B, Zheng C, Zheng C, et al: Activation of AMPK pathway by low‑dose donafenib and atorvastatin combination improves high‑fat diet‑induced metabolic dysfunction‑associated steatotic liver disease. Mol Med Rep 29: 51, 2024.
APA
Bai, Y., Chen, K., Liu, J., Wang, Y., Wang, C., Ju, S. ... Zheng, C. (2024). Activation of AMPK pathway by low‑dose donafenib and atorvastatin combination improves high‑fat diet‑induced metabolic dysfunction‑associated steatotic liver disease. Molecular Medicine Reports, 29, 51. https://doi.org/10.3892/mmr.2024.13175
MLA
Bai, Y., Chen, K., Liu, J., Wang, Y., Wang, C., Ju, S., Zhou, C., Yao, W., Xiong, B., Zheng, C."Activation of AMPK pathway by low‑dose donafenib and atorvastatin combination improves high‑fat diet‑induced metabolic dysfunction‑associated steatotic liver disease". Molecular Medicine Reports 29.3 (2024): 51.
Chicago
Bai, Y., Chen, K., Liu, J., Wang, Y., Wang, C., Ju, S., Zhou, C., Yao, W., Xiong, B., Zheng, C."Activation of AMPK pathway by low‑dose donafenib and atorvastatin combination improves high‑fat diet‑induced metabolic dysfunction‑associated steatotic liver disease". Molecular Medicine Reports 29, no. 3 (2024): 51. https://doi.org/10.3892/mmr.2024.13175
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