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Metabolic Remodeling during Liver Regeneration

Caldez, Matias J ; Van Hul, Noémi ; Koh, Hiromi W L ; Teo, Xing Qi ; Fan, Jun Jun ; Tan, Peck Yean ; Dewhurst, Matthew R ; Too, Peh Gek ; Talib, S Zakiah A and Chiang, Beatrice E , et al. (2018) In Developmental Cell 47(4). p.425-438
Abstract

Liver disease is linked to a decreased capacity of hepatocytes to divide. In addition, cellular metabolism is important for tissue homeostasis and regeneration. Since metabolic changes are a hallmark of liver disease, we investigated the connections between metabolism and cell division. We determined global metabolic changes at different stages of liver regeneration using a combination of integrated transcriptomic and metabolomic analyses with advanced functional redox in vivo imaging. Our data indicate that blocking hepatocyte division during regeneration leads to mitochondrial dysfunction and downregulation of oxidative pathways. This resulted in an increased redox ratio and hyperactivity of alanine transaminase allowing the... (More)

Liver disease is linked to a decreased capacity of hepatocytes to divide. In addition, cellular metabolism is important for tissue homeostasis and regeneration. Since metabolic changes are a hallmark of liver disease, we investigated the connections between metabolism and cell division. We determined global metabolic changes at different stages of liver regeneration using a combination of integrated transcriptomic and metabolomic analyses with advanced functional redox in vivo imaging. Our data indicate that blocking hepatocyte division during regeneration leads to mitochondrial dysfunction and downregulation of oxidative pathways. This resulted in an increased redox ratio and hyperactivity of alanine transaminase allowing the production of alanine and α-ketoglutarate from pyruvate when mitochondrial functions are impaired. Our data suggests that during liver regeneration, cell division leads to hepatic metabolic remodeling. Moreover, we demonstrate that hepatocytes are equipped with a flexible metabolic machinery able to adapt dynamically to changes during tissue regeneration.

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publishing date
type
Contribution to journal
publication status
published
subject
keywords
Animals, Hepatocytes/metabolism, Liver/metabolism, Liver Regeneration/physiology, Metabolomics/methods, Mitochondria/metabolism, Pyruvic Acid/metabolism
in
Developmental Cell
volume
47
issue
4
pages
425 - 438
publisher
Cell Press
external identifiers
  • pmid:30344111
  • scopus:85056802295
ISSN
1534-5807
DOI
10.1016/j.devcel.2018.09.020
language
English
LU publication?
no
additional info
Copyright © 2018 Elsevier Inc. All rights reserved.
id
5c008543-f8aa-47de-972a-cd3f1f7b8e5a
date added to LUP
2019-09-17 14:43:29
date last changed
2020-12-01 03:15:54
@article{5c008543-f8aa-47de-972a-cd3f1f7b8e5a,
  abstract     = {<p>Liver disease is linked to a decreased capacity of hepatocytes to divide. In addition, cellular metabolism is important for tissue homeostasis and regeneration. Since metabolic changes are a hallmark of liver disease, we investigated the connections between metabolism and cell division. We determined global metabolic changes at different stages of liver regeneration using a combination of integrated transcriptomic and metabolomic analyses with advanced functional redox in vivo imaging. Our data indicate that blocking hepatocyte division during regeneration leads to mitochondrial dysfunction and downregulation of oxidative pathways. This resulted in an increased redox ratio and hyperactivity of alanine transaminase allowing the production of alanine and α-ketoglutarate from pyruvate when mitochondrial functions are impaired. Our data suggests that during liver regeneration, cell division leads to hepatic metabolic remodeling. Moreover, we demonstrate that hepatocytes are equipped with a flexible metabolic machinery able to adapt dynamically to changes during tissue regeneration.</p>},
  author       = {Caldez, Matias J and Van Hul, Noémi and Koh, Hiromi W L and Teo, Xing Qi and Fan, Jun Jun and Tan, Peck Yean and Dewhurst, Matthew R and Too, Peh Gek and Talib, S Zakiah A and Chiang, Beatrice E and Stünkel, Walter and Yu, Hanry and Lee, Philip and Fuhrer, Tobias and Choi, Hyungwon and Björklund, Mikael and Kaldis, Philipp},
  issn         = {1534-5807},
  language     = {eng},
  month        = {11},
  number       = {4},
  pages        = {425--438},
  publisher    = {Cell Press},
  series       = {Developmental Cell},
  title        = {Metabolic Remodeling during Liver Regeneration},
  url          = {http://dx.doi.org/10.1016/j.devcel.2018.09.020},
  doi          = {10.1016/j.devcel.2018.09.020},
  volume       = {47},
  year         = {2018},
}