Metabolic Remodeling during Liver Regeneration
(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.
(Less)
- author
- publishing date
- 2018-11-19
- 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
-
- scopus:85056802295
- pmid:30344111
- 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
- 2024-09-19 09:47:14
@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}}, keywords = {{Animals; Hepatocytes/metabolism; Liver/metabolism; Liver Regeneration/physiology; Metabolomics/methods; Mitochondria/metabolism; Pyruvic Acid/metabolism}}, 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}}, }