Understanding Macrophage Complexity in Metabolic Dysfunction-Associated Steatotic Liver Disease: Transitioning from...

Area of Science:

• Hepatology
• Immunology
• Cell Biology

Background:

• Metabolic dysfunction-associated steatotic liver disease (MASLD) affects roughly 25% of the global population, encompassing metabolic dysfunction-associated fatty liver (MASL) and metabolic dysfunction-associated steatohepatitis (MASH).
• MASH is a significant risk factor for severe liver conditions like cirrhosis and hepatocellular carcinoma (HCC), imposing substantial healthcare burdens.
• The liver's immune microenvironment, particularly hepatic macrophages, plays a critical role in MASLD pathogenesis, influencing disease progression and outcomes.

Purpose of the Study:

• To review the multifaceted involvement of hepatic macrophages in the progression of MASLD.
• To integrate traditional understandings of macrophage function with recent single-cell and spatial analyses in MASLD.
• To highlight the heterogeneity and plasticity of macrophage populations in MASLD and their therapeutic implications.

Main Methods:

• Review of existing literature on hepatic macrophages and MASLD.
• Analysis of recent technological advancements, including single-cell sequencing and spatial transcriptomics.
• Synthesis of data from traditional M1/M2 macrophage paradigms and novel findings.

Main Results:

• Hepatic macrophages exhibit significant heterogeneity and plasticity in MASLD, challenging the simplistic M1/M2 classification.
• Both detrimental and beneficial macrophage phenotypes coexist and are dynamically regulated during MASLD progression.
• Macrophage ontogeny and diverse functional states are critical considerations for therapeutic strategies.

Conclusions:

• Hepatic macrophages are central players in MASLD, with complex and dynamic roles.
• Targeting specific macrophage phenotypes and understanding their heterogeneity offers promising therapeutic avenues for MASLD.
• Further research is needed to address unresolved questions regarding macrophage involvement in MASLD progression.