Updated mechanisms of MASLD pathogenesis.

Area of Science:

• Hepatology
• Metabolic Diseases
• Microbiome Research

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing globally, linked to lifestyle factors like over-nutrition and inactivity.
• MASLD is associated with obesity and metabolic syndromes, necessitating a deeper understanding of its pathogenesis.
• Hepatic lipid accumulation can lead to lipotoxicity, endoplasmic reticulum stress, oxidative stress, organelle dysfunction, and ferroptosis, driving MASLD and its progression to MASH.

Purpose of the Study:

• To summarize and evaluate the roles of lipotoxicity, ferroptosis, and gut microbes in MASLD pathogenesis.
• To elucidate the underlying mechanisms of these factors in MASLD development.
• To outline current advances and challenges in MASLD treatment.

Main Methods:

• Literature review and synthesis of existing research on MASLD.
• Evaluation of the mechanisms linking lipotoxicity, ferroptosis, and gut dysbiosis to liver disease.
• Analysis of current therapeutic strategies and their limitations.

Main Results:

• Hepatic lipotoxicity, ferroptosis, and gut microbial dysbiosis are key contributors to MASLD development.
• These factors mediate cellular stress and organelle dysfunction, promoting liver steatosis and inflammation.
• The complex interplay of these elements presents significant challenges for developing effective pharmacological therapies.

Conclusions:

• Targeting lipotoxicity, ferroptosis, and gut microbiota represents a promising avenue for MASLD intervention.
• Further research is needed to overcome the challenges in clinical trials and identify effective treatments.
• Understanding these pathogenic mechanisms is crucial for developing novel therapeutic strategies for MASLD.