Abnormalities of intracellular organelles in metabolic dysfunction-associated steatotic disease.

Abstract

BACKGROUND: The concept of metabolic dysfunction-associated steatotic disease (MASLD) is increasingly being recognized. The mechanisms contributing to hepatocellular injury include oxidative stress owing to mitochondrial dysfunction, endoplasmic reticulum (ER) stress owing to abnormal protein accumulation in the rough ER, and disruption of cellular homeostasis and metabolic regulation to autophagic dysfunction. However, the morphological abnormalities of these intracellular organelles remain unclear. METHODS: Liver tissues from model mice of MASLD, patients with MASLD, and respective controls were subjected to histopathological examination using light microscopy, and intracellular organelles were analyzed via transmission electron microscopy (TEM). RESULTS: In model mice of MASLD, the progression of MASLD pathology was associated with abnormalities in mitochondria, glycogen granules, and rough ER. Based on these findings, the electron microscopic observations of these intracellular organelles were classified, weighted, and evaluated in liver tissues of patients with MASLD. The electron microscopic findings were significantly relatively frequent in patients with MASLD and correlated with existing histopathological scoring. CONCLUSIONS: Using TEM, we identified characteristic abnormalities in intracellular organelles specific to MASLD. These findings contribute to the understanding of the mechanisms underlying hepatocellular injury in MASLD.