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Maladaptive regeneration and metabolic dysfunction associated steatotic liver disease: Common mechanisms and

Dandan Wu1, Stan F J van de Graaf1

  • 1Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Gastroenterology, Endocrinology and Metabolism (AGEM), Amsterdam University Medical Centers, the Netherlands.

Biochemical Pharmacology
|July 18, 2024
PubMed

Insights

Metabolic dysfunction associated steatotic liver disease impairs liver regeneration by affecting key pathways. Targeting these shared mechanisms may improve both steatohepatitis and liver repair capacity.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Regenerative Medicine

Background:

  • Normal liver regeneration is robust but impaired in steatotic livers.
  • Metabolic dysfunction associated steatotic liver disease (MASLD) shares mechanisms with liver regeneration.
  • Key regeneration pathways (HGF/c-Met, EGFR, Wnt/β-catenin, Hippo/YAP-TAZ) are altered in MASLD.

Purpose of the Study:

  • To review common molecular pathways linking MASLD and liver regeneration.
  • To identify therapeutic strategies for ameliorating steatohepatitis and enhancing regeneration in steatotic livers.
  • To explore novel applications of ex-vivo liver perfusion for therapeutic interventions.

Main Methods:

  • Literature review focusing on molecular pathways in MASLD and liver regeneration.
  • Analysis of therapeutic targets for MASH (Metabolic dysfunction-associated steatohepatitis) and their role in hepatocyte proliferation.
  • Discussion of emerging techniques like ex-vivo normothermic liver perfusion.

Main Results:

  • MASLD affects critical liver regeneration pathways.
  • Therapeutic targets for MASH, including Thyroid Hormone receptors, GLP1, FXR, PPARs, and FGF21, also influence hepatocyte proliferation.
  • Ex-vivo liver perfusion presents new therapeutic possibilities for steatotic livers.

Conclusions:

  • Understanding shared molecular pathways is crucial for developing synergistic treatments for MASLD and impaired regeneration.
  • Targeting these pathways could improve outcomes for patients with steatotic liver disease.
  • Advanced perfusion techniques may enable novel therapeutic strategies for steatotic donor livers or segments.
Keywords:
Bile saltFGF21FXRHepatectomyLiver resectionMASHMASLDPPARThyroid HormoneTransplantation

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