Ectopic localization of autophagosome in fatty liver is a key factor for liver regeneration

Research output: Contribution to journalArticle

Abstract

Autophagy has a critical role in liver regeneration. However, no studies have demonstrated autophagic flux in the regenerating fatty liver. The aim of this study was to clarify the dynamics of autophagy in the regeneration of the fatty liver. Following 70% partial hepatectomy (PH) in db/db fatty mice, which is a non-alcoholic fatty liver disease (NAFLD) model, we investigated the survival rate and recovery of liver volume. Histological examination of the regenerating liver was examined using electron microscopy. The 7-day survival rate after PH in db/db mice was 20%, which was significantly lower than that in control mice (P<.01). Liver regeneration within 48 h after PH was significantly impaired in db/db mice (P<.05). The number of proliferating cell nuclear antigen (PCNA) positive cells and the expression levels of cell-cycle markers cyclins D, E, and A were lower in db/db mice compared with controls. In the regenerating liver, LC3-II level was higher in db/db mice, but p62 expression was increased and cathepsin D expression, a marker of autophagolysosome proteolysis, was decreased compared with controls. Additionally, electronic microscopy revealed that autophagosomes during liver regeneration in db/db mice were mainly located in lipid droplets. Our findings indicate that the different localization of autophagosomes in db/db mice compared with controls led to impairment of liver regeneration in the fatty liver.

Original languageEnglish
Pages (from-to)24-34
Number of pages11
JournalOrganogenesis
Volume15
Issue number1
DOIs
Publication statusPublished - Jan 2 2019

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Liver Regeneration
Fatty Liver
Liver
Hepatectomy
Autophagy
Cyclin D
Cyclin A
Cyclin E
Cathepsin D
Autophagosomes
Proliferating Cell Nuclear Antigen
Cells
Proteolysis
Regeneration
Microscopy
Electron Microscopy
Cell Cycle
Antigens
Lipids
Electron microscopy

All Science Journal Classification (ASJC) codes

  • Biomedical Engineering
  • Embryology
  • Developmental Biology
  • Transplantation

Cite this

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title = "Ectopic localization of autophagosome in fatty liver is a key factor for liver regeneration",
abstract = "Autophagy has a critical role in liver regeneration. However, no studies have demonstrated autophagic flux in the regenerating fatty liver. The aim of this study was to clarify the dynamics of autophagy in the regeneration of the fatty liver. Following 70{\%} partial hepatectomy (PH) in db/db fatty mice, which is a non-alcoholic fatty liver disease (NAFLD) model, we investigated the survival rate and recovery of liver volume. Histological examination of the regenerating liver was examined using electron microscopy. The 7-day survival rate after PH in db/db mice was 20{\%}, which was significantly lower than that in control mice (P<.01). Liver regeneration within 48 h after PH was significantly impaired in db/db mice (P<.05). The number of proliferating cell nuclear antigen (PCNA) positive cells and the expression levels of cell-cycle markers cyclins D, E, and A were lower in db/db mice compared with controls. In the regenerating liver, LC3-II level was higher in db/db mice, but p62 expression was increased and cathepsin D expression, a marker of autophagolysosome proteolysis, was decreased compared with controls. Additionally, electronic microscopy revealed that autophagosomes during liver regeneration in db/db mice were mainly located in lipid droplets. Our findings indicate that the different localization of autophagosomes in db/db mice compared with controls led to impairment of liver regeneration in the fatty liver.",
author = "Yoshihiro Matsumoto and Tomoharu Yoshizumi and Takeo Toshima and kazuki takeishi and Takasuke Fukuhara and shinji itoh and Toru Ikegami and Yuji Soejima and Masaki Mori",
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