Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Oct;43(10):2309-2319.
doi: 10.1111/liv.15665. Epub 2023 Jul 4.

Endothelial autophagy is not required for liver regeneration after partial hepatectomy in mice with fatty liver

Adel Hammoutene  1   2 , Marion Tanguy  1   2 , Mélanie Calmels  1 , Riccardo Pravisani  3 , Miguel Albuquerque  2   4 , Christophe Casteleyn  5 , Lotfi Slimani  6   7 , Jeremy Sadoine  6   7 , Chantal M Boulanger  1 , Valérie Paradis  2   4 , Hélène Gilgenkrantz  2 , Pierre-Emmanuel Rautou  1   2   8
Affiliations

Endothelial autophagy is not required for liver regeneration after partial hepatectomy in mice with fatty liver

Adel Hammoutene et al. Liver Int. 2023 Oct.

Abstract

Background & aims: Patients with non-alcoholic fatty liver disease (NAFLD) have impaired liver regeneration. Liver endothelial cells play a key role in liver regeneration. In non-alcoholic steatohepatitis (NASH), liver endothelial cells display a defect in autophagy, contributing to NASH progression. We aimed to determine the role of endothelial autophagy in liver regeneration following liver resection in NAFLD.

Methods: First, we assessed autophagy in primary endothelial cells from wild type mice fed a high fat diet and subjected to partial hepatectomy. Then, we assessed liver regeneration after partial hepatectomy in mice deficient (Atg5lox/lox ;VE-cadherin-Cre+ ) or not (Atg5lox/lox ) in endothelial autophagy and fed a high fat diet. The role of endothelial autophagy in liver regeneration was also assessed in ApoE-/- hypercholesterolemic mice and in mice with NASH induced by methionine- and choline-deficient diet.

Results: First, autophagy (LC3II/protein) was strongly increased in liver endothelial cells following hepatectomy. Then, we observed at 40 and 48 h and at 7 days after partial hepatectomy, that Atg5lox/lox ;VE-cadherin-Cre+ mice fed a high fat diet had similar liver weight, plasma AST, ALT and albumin concentration, and liver protein expression of proliferation (PCNA), cell-cycle (Cyclin D1, BrdU incorporation, phospho-Histone H3) and apoptosis markers (cleaved Caspase-3) as Atg5lox/lox mice fed a high fat diet. Same results were obtained in ApoE-/- and methionine- and choline-deficient diet fed mice, 40 h after hepatectomy.

Conclusion: These results demonstrate that the defect in endothelial autophagy occurring in NASH does not account for the impaired liver regeneration occurring in this setting.

Keywords: LSECs; NAFLD; autophagy; hepatectomy; liver regeneration.

PubMed Disclaimer

Comment in

References

REFERENCES

    1. Karlsen TH, Sheron N, Zelber-Sagi S, et al. The EASL-Lancet Liver Commission: protecting the next generation of Europeans against liver disease complications and premature mortality. Lancet. 2022;399:61-116. doi:10.1016/S0140-6736(21)01701-3
    1. Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell. 2021;184:2537-2564. doi:10.1016/j.cell.2021.04.015
    1. Ioannou GN. Epidemiology and risk-stratification of NAFLD-associated HCC. J Hepatol. 2021;75:1476-1484. doi:10.1016/j.jhep.2021.08.012
    1. Allaire M, Gilgenkrantz H. The impact of steatosis on liver regeneration. Horm Mol Biol Clin Invest. 2018;41:20180050. doi:10.1515/hmbci-2018-0050
    1. Huang R, Zhang X, Gracia-Sancho J, Xie W-F. Liver regeneration: cellular origin and molecular mechanisms. Liver Int. 2022;42:1486-1495. doi:10.1111/liv.15174

Publication types