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Intricate interplay between cell metabolism and necroptosis regulation in metabolic dysfunction-associated steatotic liver disease: A narrative review.

Marta Bento AfonsoJan Caira DavidMariana Isabel AlvesAndré Anastácio SantosGonçalo CampinoVlad RatziuJérémie GautheronCecília Maria Pereira Rodrigues
Published in: Metabolism: clinical and experimental (2024)
Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), encompasses a progressive spectrum of liver conditions, ranging from steatosis to metabolic dysfunction-associated steatohepatitis, characterised by hepatocellular death and inflammation, potentially progressing to cirrhosis and/or liver cancer. In both experimental and human MASLD, necroptosis-a regulated immunogenic necrotic cell death pathway-is triggered, yet its exact role in disease pathogenesis remains unclear. Noteworthy, necroptosis-related signalling pathways are emerging as key players in metabolic reprogramming, including lipid and mitochondrial metabolism. Additionally, metabolic dysregulation is a well-established contributor to MASLD development and progression. This review explores the intricate interplay between cell metabolism and necroptosis regulation and its impact on MASLD pathogenesis. Understanding these cellular events may offer new insights into the complexity of MASLD pathophysiology, potentially uncovering therapeutic opportunities and unforeseen metabolic consequences of targeting necroptosis.
Keyphrases
  • oxidative stress
  • cell death
  • single cell
  • endothelial cells
  • multiple sclerosis
  • fatty acid
  • metabolic syndrome
  • drug delivery
  • high fat diet
  • density functional theory