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.