Lipotoxicity-driven metabolic dysfunction-associated steatotic liver disease (MASLD)

Area of Science:

• Hepatology and Metabolic Diseases
• Molecular Mechanisms of Liver Injury

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over a third of the population, progressing from steatosis to cirrhosis.
• MASLD is a major risk factor for liver failure, cancer, and mortality.
• Pathogenesis involves metabolic, environmental, microbial, and genetic factors.

Purpose of the Study:

• To comprehensively review the role of lipotoxicity in MASLD pathogenesis.
• To discuss key lipid species, molecular mechanisms, and cell-specific effects.
• To highlight potential therapeutic strategies targeting lipotoxicity and lipid metabolism.

Main Methods:

• Literature review of studies on lipotoxicity in MASLD.
• Analysis of lipid species, molecular pathways, and cellular responses.
• Evaluation of emerging therapeutic targets.

Main Results:

• Dysregulated lipid composition generates toxic species, inducing lipotoxicity and cellular stress.
• Lipotoxicity activates cell death pathways, leading to inflammation, fibrosis, and carcinogenesis.
• Specific lipid species and their metabolic pathways are critical drivers of MASLD progression.

Conclusions:

• Lipotoxicity is a central mechanism in MASLD pathogenesis, driving liver damage and progression.
• Understanding cell-specific lipotoxic effects is crucial for targeted therapies.
• Modulating lipotoxicity and lipid metabolism offers promising therapeutic avenues for MASLD.