Liver regeneration: metabolic and epigenetic regulation

Abstract

The liver is bestowed with an extraordinary regenerative capability, which is accomplished by a well-coordinated cellular and molecular response at different phases of regeneration. Metabolism, as the primary function of liver, displays various alterations as a consequence of hepatic insufficiency from an injury. These metabolic perturbations are physiologically relevant for promoting hepatocellular proliferation and regeneration. On the other hand, proliferation of otherwise quiescent hepatocytes and accompanied regeneration are regulated by transient, but precisely regulated transcriptional reprogramming. This phase-cell-and time-specific gene expression is controlled by epigenetic mechanisms. Hence, both metabolic and epigenetic changes regulate liver regeneration events. But the cross-talk between metabolic and epigenetic changes for a successful liver regeneration needs to be explored. Since most of the enzymatic players of epigenetic mechanisms rely upon metabolites for their substrates and co-factors, we expect a highly coordinated interdependence between metabolism and epigenetics during liver regeneration too. In the present review, we discuss various metabolic and epigenetic regulatory mechanisms for liver regeneration, and put forward the possible metabolic-epigeneticliver regeneration link for a better understanding of the process and identification of novel targets for liver-related diseases in clinical settings.

Temporal-spatially metabolic reprogramming rewires the H3K27ac landscape to enable the initiation of liver regeneration

“…It is also worth noting that previous studies have indirectly demonstrated that FAO effectively promotes the process of liver regeneration by reshaping the balance between the demand for and supply of fatty acids by inhibiting PTEN or providing ATP and carnitine (29)(30)(31). Suppressed transient lipid droplet accumulation after PHx resulted in impairment of liver regeneration, with biological implications linked to adiposederived hormones like adiponectin and leptin, or ATP production (32,33). A most recent publication also suggested that Acetyl-CoA provided by FAO can promote histone acetylation during liver regeneration, but the relevant research was conducted at least 2 days after PHx, which were not be able to provide 28 sufficient evidence in explaining the role of FAO in the initiation of liver regeneration (34).…”

“…All data associated with this study are included within the main text or the Supplementary information. Raw RNA-seq data, Untargeted Metabolomics data, Spatial Metabolomics data, and CUT&Tag data generated in the present 33 study have been deposited at NCBI GEO databank and other public databases and will be publicly available as of the date of publication. Other data reported in this paper will be shared by the corresponding author upon request.…”