Open Access

Integrated multi‑omics analysis of liver metabolic dysregulation in ACE2 knockout mice

  • Authors:
    • Shuai Xiao
    • Jinxiu Guo
    • Bo Yu
    • Shiyuan Zhao
    • Yicun Shang
    • Ni Li
    • Jiyao Cui
    • Fangqiang Song
    • Pei Jiang
  • View Affiliations

  • Published online on: July 3, 2025     https://doi.org/10.3892/ijmm.2025.5575
  • Article Number: 134
  • Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study systematically investigated the impact of angiotensin‑converting enzyme 2‑knockout (ACE2KO) on hepatic metabolic homeostasis and its molecular mechanisms using integrated transcriptomic, proteomic and metabolomic profiling. ACE2KO exacerbated hepatic lipid accumulation, as evidenced by elevated total cholesterol and triglyceride levels, while disrupting the renin‑angiotensin system equilibrium via increased angiotensin II levels and reduced angiotensin‑(1‑7) levels. Histopathological analysis revealed hepatocyte edema, vacuolar degeneration and inflammatory infiltration in the ACE2KO mice. Multi‑omics integration revealed systemic metabolic dysregulation. Transcriptomics identified 1,004 differentially expressed genes, including lipid metabolism regulators (Scd1 and Fabp1) and circadian rhythm modulators (Arntl and Cry1), proteomics identified 191 differentially expressed proteins associated with interferon signaling activation (Oas1a and Rsad2) and lipid synthesis suppression (Scd1 and Fasn), and metabolomics highlighted 193 differentially expressed metabolites indicative of bile acid dysregulation, glutathione redox imbalance and amino acid metabolism anomalies. Cross‑omics analysis indicated that ACE2 is a key regulator of metabolic homeostasis. Its absence causes systematic metabolic disorders, including lipid metabolism disorder, amino acid metabolic imbalance and detoxification dysfunction. These findings comprehensively delineated the multifaceted role of ACE2 in hepatic metabolic homeostasis, and provided mechanistic insights into and therapeutic targets for ACE2‑associated liver diseases.
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September-2025
Volume 56 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Copy and paste a formatted citation
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Spandidos Publications style
Xiao S, Guo J, Yu B, Zhao S, Shang Y, Li N, Cui J, Song F and Jiang P: Integrated multi‑omics analysis of liver metabolic dysregulation in ACE2 knockout mice. Int J Mol Med 56: 134, 2025.
APA
Xiao, S., Guo, J., Yu, B., Zhao, S., Shang, Y., Li, N. ... Jiang, P. (2025). Integrated multi‑omics analysis of liver metabolic dysregulation in ACE2 knockout mice. International Journal of Molecular Medicine, 56, 134. https://doi.org/10.3892/ijmm.2025.5575
MLA
Xiao, S., Guo, J., Yu, B., Zhao, S., Shang, Y., Li, N., Cui, J., Song, F., Jiang, P."Integrated multi‑omics analysis of liver metabolic dysregulation in ACE2 knockout mice". International Journal of Molecular Medicine 56.3 (2025): 134.
Chicago
Xiao, S., Guo, J., Yu, B., Zhao, S., Shang, Y., Li, N., Cui, J., Song, F., Jiang, P."Integrated multi‑omics analysis of liver metabolic dysregulation in ACE2 knockout mice". International Journal of Molecular Medicine 56, no. 3 (2025): 134. https://doi.org/10.3892/ijmm.2025.5575