Metabolic Remodeling during Liver Regeneration Caldez, Matias J. et al. Developmental Cell, Volume 47, Issue 4, 425 - 438.e5
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.
This work is supported by the Biomedical Research Council , Agency for Science, Technology and Research (A∗STAR) to P.K., H.Y., P.L., W.S., and H.C.; SINGA (Singapore InterNational Graduate Award) to M.J.C.; the Institute of Bioengineering and Nanotechnology , A∗STAR (Project Number 1334i00051 to H.Y.); NMRC ( R-185-000-294-511 to H.Y.); SMART BioSyM and Mechanobiology Institute of Singapore ( R-714-001-003-271 to H.Y.); and the Biomedical Research Council – Joint Council Office Grant ( 1231AFG031 to P.K. and P.L.).
The full paper is available for download at the publisher's URL: https://doi.org/10.1016/j.devcel.2018.09.020