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Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Macrophages in MASLD: from inflammatory and metabolic crosstalk to exercise intervention
Yi Sun1,2
1Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, East China Normal University, Shanghai, China.
Abstract:
Metabolic dysfunction-associated steatotic liver disease (MASLD) places a heavy burden on public health, with no approved therapies. Hepatic macrophages are central to MASLD pathogenesis. In this review, the clinical spectrum of MASLD and the heterogeneity of liver macrophages are summarized, covering classical M1/M2 polarization and novel subsets identified by single-cell transcriptomics. Beyond the well-recognized inflammatory roles, non-inflammatory mechanisms through which macrophages contribute to insulin resistance and steatosis are also highlighted. Importantly, a novel framework is established, which positions exercise as a systemic integrator. In this framework, exercise simultaneously dampens adipose-derived pro-inflammatory inputs while amplifying muscle-derived protective signals, thereby rewiring multi-organ communication to reprogram hepatic macrophage function. Finally, evidence is integrated, showing that exercise re-polarizes macrophages, reshapes intrahepatic immune landscape, and mediates muscle-liver communication through exercise-induced factors. Together, this review provides a framework for understanding macrophage-centered mechanisms in MASLD, and highlights lifestyle intervention as a promising therapeutic strategy.
Insights
Exercise can reprogram liver macrophages to combat metabolic dysfunction-associated steatotic liver disease (MASLD). This lifestyle intervention offers a promising therapeutic strategy for MASLD by modulating immune responses and improving multi-organ communication.
Area of Science:
- Hepatology
- Immunology
- Metabolic Diseases
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern lacking approved treatments.
- Hepatic macrophages play a critical role in MASLD development and progression.
- Understanding macrophage heterogeneity and function is key to developing MASLD therapies.
Purpose of the Study:
- To review the clinical aspects of MASLD and the diverse roles of liver macrophages.
- To explore non-inflammatory mechanisms of macrophage contribution to MASLD.
- To present a novel framework positioning exercise as a regulator of hepatic macrophage function.
Main Methods:
- Review of existing literature on MASLD pathogenesis and macrophage biology.
- Analysis of classical M1/M2 polarization and novel macrophage subsets via single-cell transcriptomics.
- Integration of evidence on exercise-induced systemic effects on multi-organ communication.
Main Results:
- MASLD involves complex macrophage heterogeneity beyond classical polarization.
- Macrophages contribute to insulin resistance and steatosis through non-inflammatory pathways.
- Exercise acts as a systemic integrator, dampening inflammation and enhancing protective signals.
Conclusions:
- Exercise reprograms hepatic macrophages, reshaping the intrahepatic immune environment.
- Exercise mediates protective muscle-liver communication through specific factors.
- Lifestyle interventions, particularly exercise, represent a promising therapeutic avenue for MASLD.
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