Related Experiment Video
Updated: Jun 19, 2025
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Lysozyme 1 Inflamed CCR2+ Macrophages Promote Obesity-Induced Cardiac Dysfunction
Lai Zhang1,2,3, Huian Han1,2, Andi Xu4
1Department of Pathophysiology (L.Z., H.H., S.F., J.Z., W.C., Y.Y., J.L., H.B., J.B., X.Z., X.L., Q.Y., H.Z., Q.C.), Nanjing Medical University, Jiangsu, China.
Insights
Obesity triggers cardiac inflammation via CCR2+ macrophages transitioning to a pro-inflammatory state. Lysozyme 1 activates NF-κB signaling, driving heart dysfunction, and may be a therapeutic target.
Area of Science:
- Immunology
- Cardiovascular Biology
- Metabolic Diseases
Background:
- Macrophages play a critical role in obesity-associated cardiovascular diseases, characterized by inflammation.
- The precise mechanisms of macrophage involvement in obesity-induced cardiac inflammation remain unclear.
- This study investigates key macrophage populations and molecular pathways in obesity-related cardiac dysfunction.
Purpose of the Study:
- To identify the specific macrophage population driving obesity-induced cardiac dysfunction.
- To elucidate the molecular mechanisms underlying macrophage-mediated cardiac inflammation in obesity.
- To explore the role of lysozyme 1 in obesity-induced cardiac inflammation.
Main Methods:
- Single-cell RNA-sequencing of cardiac macrophages to analyze heterogeneity.
- Genetic ablation of C-C chemokine receptor 2 (CCR2)+ macrophages to assess functional impact.
- Molecular assays including ChIP-PCR and luciferase assays to define signaling pathways.
Main Results:
- Cardiac macrophages, specifically CCR2+ cells, shift from homeostasis to a pro-inflammatory phenotype in obesity.
- Ablation of CCR2+ macrophages or CCR2 itself ameliorates obesity-induced cardiac dysfunction.
- The CCR2/activating transcription factor 3/lysozyme 1/NF-κB signaling axis mediates this inflammatory shift, with lysozyme 1 activating NF-κB.
Conclusions:
- Lysozyme 1 acts as a transcription activator for NF-κB, promoting inflammation and cardiac dysfunction in obesity.
- Targeting lysozyme 1 could offer a diagnostic and therapeutic strategy for obesity-induced heart disease.
Background:
Macrophages are key players in obesity-associated cardiovascular diseases, which are marked by inflammatory and immune alterations. However, the pathophysiological mechanisms underlying macrophage's role in obesity-induced cardiac inflammation are incompletely understood. Our study aimed to identify the key macrophage population involved in obesity-induced cardiac dysfunction and investigate the molecular mechanism that contributes to the inflammatory response.
Methods:
In this study, we used single-cell RNA-sequencing analysis of Cd45+CD11b+F4/80+ cardiac macrophages to explore the heterogeneity of cardiac macrophages. The CCR2+ (C-C chemokine receptor 2) macrophages were specifically removed by a dual recombinase approach, and the macrophage CCR2 was deleted to investigate their functions. We also performed cleavage under target and tagmentation analysis, chromatin immunoprecipitation-polymerase chain reaction, luciferase assay, and macrophage-specific lentivirus transfection to define the impact of lysozyme C in macrophages on obesity-induced inflammation.
Results:
We find that the Ccr2 cluster undergoes a functional transition from homeostatic maintenance to proinflammation. Our data highlight specific changes in macrophage behavior during cardiac dysfunction under metabolic challenge. Consistently, inducible ablation of CCR2+CX3CR1+ macrophages or selective deletion of macrophage CCR2 prevents obesity-induced cardiac dysfunction. At the mechanistic level, we demonstrate that the obesity-induced functional shift of CCR2-expressing macrophages is mediated by the CCR2/activating transcription factor 3/lysozyme 1/NF-κB (nuclear factor kappa B) signaling. Finally, we uncover a noncanonical role for lysozyme 1 as a transcription activator, binding to the RelA promoter, driving NF-κB signaling, and strongly promoting inflammation and cardiac dysfunction in obesity.
Conclusions:
Our findings suggest that lysozyme 1 may represent a potential target for the diagnosis of obesity-induced inflammation and the treatment of obesity-induced heart disease.
Related Concept Videos
01:38Inflammation
01:24Obesity