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Molecular characterization of microvesicular and macrovesicular steatosis shows widespread differences in metabolic pathways

Lipids 54(1):109-115, 2019

Kristiansen MNB, Veidal SS, Christoffersen C, Jelsing J, Rigbolt KTG

Abstract
Simple steatosis is the hallmark of nonalcoholic fatty liver disease (NAFLD), characterized by lipid accumulation within hepatocytes as either microvesicular or macrovesicular lipid droplets. This study employed a combination of laser capture microdissection (LCM) and RNA sequencing (RNAseq) to characterize murine gene expression in nonsteatotic, microsteatotic, and macrosteatotic compartments collected from the same liver.

Key findings:

  • Microvesicular steatosis represents an intermediate state between nonsteatotic and macrovesicular steatosis, displaying widespread and pronounced regulation of metabolic genes involved in lipid export, gluconeogenesis, and de novo lipogenesis.
  • Expression differences were observed in key enzymes, including:
    • Fatty acid synthase (FASN) (de novo lipogenesis)
    • Fructose 1,6-bisphosphatase (FBP1) (gluconeogenesis)
    • Apolipoprotein C-III (APOC3) (lipid transport)
  • Increased expression of genes involved in lipid particle formation provided a molecular description of the fusion of microsteatotic lipid compartments, resulting in the formation of macrosteatotic cells with a single enlarged lipid droplet.

In conclusion, this study offers a comprehensive transcriptomic analysis, highlighting distinct molecular profiles between micro- and macrovesicular steatosis and providing insights into the progression of NAFLD at the cellular level.

 

Subjects
Therapeutic AreaMouseMethod/EndpointSpeciesAMLN DIO-MASH mouseBioinformaticsMetabolic dysfunction-associated steatohepatitisRNA sequencing

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