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Updated: May 20, 2026
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Integrated multi-omics identifies distinct macrophage alterations during progression of metabolic
Markus Boesch1,2,3,4, Seray Anak2, Dania El Abyad2
1Laboratory of Liver Immunology, Leuven Center of Molecular Liver Sciences, Hepatology Research Unit, CHROMETA Department, KU Leuven, Leuven, Belgium.
Abstract:
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a chronic condition impacting over 30% population, yet the dynamic changes in macrophage composition from steatosis to steatohepatitis (metabolic dysfunction-associated steatohepatitis, MASH) remain unclear. Here, by integrating single-nucleus transcriptomics, spatial multi-omics and proteomics on human samples, we delineate the evolving landscape of hepatic macrophages across the MASLD spectrum. Our analysis reveals a progressive depletion of Kupffer cells accompanied by the emergence of diverse, phenotypically distinct macrophage subsets. Spatial multi-omics further demonstrates that disease progression toward MASH is marked by an accumulation of antigen-presenting, phagocytic GPNMB+ macrophages, supported by IL32-producing hepatocytes. These macrophages showed an adaptive metabolic and pro-inflammatory phenotype that is tightly regulated by both spatial context and disease stage. Identified macrophage markers enable patient stratification by disease activity and its stage across independent clinical cohorts. Our study sheds light on the diversity of macrophage identities and metabolic-adaptive phenotypes during the progression of MASLD.
Insights
Metabolic dysfunction-associated steatotic liver disease (MASLD) involves changing liver macrophages. This study reveals new macrophage types emerge as MASLD progresses to metabolic dysfunction-associated steatohepatitis (MASH).
Area of Science:
- Hepatology
- Immunology
- Systems Biology
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over 30% of the population.
- The dynamic changes in hepatic macrophage composition during MASLD progression to metabolic dysfunction-associated steatohepatitis (MASH) are not fully understood.
Purpose of the Study:
- To delineate the evolving landscape of hepatic macrophages across the MASLD spectrum.
- To identify macrophage subsets and their phenotypes associated with disease progression.
Main Methods:
- Integration of single-nucleus transcriptomics, spatial multi-omics, and proteomics on human liver samples.
- Analysis of macrophage populations and their spatial distribution in relation to disease stage.
Main Results:
- Progressive depletion of Kupffer cells observed during MASLD progression.
- Emergence of diverse, phenotypically distinct macrophage subsets, including GPNMB+ macrophages.
- Spatial multi-omics identified accumulation of antigen-presenting, phagocytic GPNMB+ macrophages in MASH, supported by IL32-producing hepatocytes.
- Macrophages exhibited adaptive metabolic and pro-inflammatory phenotypes regulated by spatial context and disease stage.
- Identified macrophage markers enabled patient stratification by disease activity and stage.
Conclusions:
- Hepatic macrophage populations undergo significant diversification during MASLD progression.
- Specific macrophage subsets, like GPNMB+ macrophages, are key players in MASH pathogenesis.
- Macrophage phenotypes are metabolically adaptive and spatially regulated, offering potential biomarkers for MASLD and MASH.
