Macrophage functional diversity in NAFLD - more than inflammation

Area of Science:

• Immunology
• Hepatology
• Genomics

Background:

• Macrophages in the liver, primarily Kupffer cells, are crucial for immune regulation and detoxification.
• Non-alcoholic fatty liver disease (NAFLD) involves a spectrum of liver conditions, including non-alcoholic steatohepatitis (NASH), driven by obesity and insulin resistance.
• NASH is a prevalent condition lacking approved treatments, highlighting the need for understanding its pathogenesis.

Purpose of the Study:

• To review the turnover and function of liver macrophages (Kupffer cells and monocyte-derived) in homeostasis and NAFLD, with a focus on NASH.
• To highlight recent advances in understanding liver macrophage heterogeneity using single-cell RNA sequencing (scRNA-seq).
• To explore hepatic macrophage functions beyond their traditional inflammatory roles in NAFLD/NASH progression.

Main Methods:

• Review of existing literature on liver macrophage biology.
• Analysis of single-cell RNA sequencing (scRNA-seq) data from the past five years.
• Examination of macrophage populations in both healthy and NAFLD/NASH states.

Main Results:

• scRNA-seq has significantly advanced the understanding of liver macrophage diversity and heterogeneity.
• Liver macrophages exhibit diverse phenotypes and functions influenced by origin, location, and disease context.
• Hepatic macrophages play multifaceted roles in NAFLD and NASH pathogenesis, extending beyond inflammation.

Conclusions:

• Liver macrophage diversity is critical for understanding NAFLD and NASH.
• Recent scRNA-seq studies have unveiled novel functions of hepatic macrophages in metabolic liver disease.
• Targeting specific liver macrophage populations may offer therapeutic strategies for NASH.