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Updated: Jun 21, 2025
Isolation, Characterization, and Purification of Macrophages from Tissues Affected by Obesity-related Inflammation
Published on: April 3, 2017
Modulation of cardiac resident macrophages immunometabolism upon high-fat-diet feeding in mice
Simeng Zhu1, Yujia Liu2, Guofang Xia1
1Department of Cardiology, Sixth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Insights
High-fat diets cause obesity and heart dysfunction by altering cardiac resident macrophages. These immune cells show metabolic and inflammatory changes, contributing to heart disease.
Area of Science:
- Cardiovascular Biology
- Immunology
- Metabolic Syndrome
Background:
- High-fat diets (HFD) induce obesity and metabolic disorders, increasing cardiovascular disease risk.
- Cardiac resident macrophages are crucial for heart homeostasis but can be dysregulated by HFD.
- Understanding HFD-induced changes in these macrophages is key to addressing cardiac dysfunction.
Purpose of the Study:
- To investigate the transcriptional and functional alterations in cardiac resident macrophages of mice fed a high-fat diet.
- To elucidate the molecular mechanisms underlying HFD-induced cardiac dysfunction.
Main Methods:
- Mice were fed a high-fat diet (HFD) or normal chow diet (NCD) for 16 weeks.
- Cardiac function was assessed using echocardiography.
- Cardiac resident CCR2-negative macrophages were isolated and subjected to Smart sequencing.
- Bioinformatics analyses (GO, KEGG, GSEA) were performed to identify transcriptional and functional changes.
Main Results:
- HFD induced obesity, hyperlipidemia, cardiac fibrosis, and diastolic dysfunction.
- Smart sequencing revealed significant metabolic dysregulation, particularly in lipid-related genes and pathways.
- Cardiac resident macrophages exhibited altered expression of antigen-presentation genes (e.g., Ctsf) and changes in inflammatory pathways (NF-κB, complement cascades).
- Gene Ontology analysis indicated specific organelle enrichment trends.
Conclusions:
- High-fat diet feeding leads to intertwined metabolic and inflammatory dysregulation in cardiac resident macrophages.
- These changes in macrophages contribute to HFD-induced cardiac dysfunction.
- Further investigation into organelle crosstalk may reveal novel therapeutic targets.
Background:
A high-fat diet (HFD) contributes to various metabolic disorders and obesity, which are major contributors to cardiovascular disease. As an essential regulator for heart homeostasis, cardiac resident macrophages may go awry and contribute to cardiac pathophysiology upon HFD. Thus, to better understand how HFD induced cardiac dysfunction, this study intends to explore the transcriptional and functional changes in cardiac resident macrophages of HFD mice.
Methods:
C57BL/6J female mice that were 6 weeks old were fed with HFD or normal chow diet (NCD) for 16 weeks. After an evaluation of cardiac functions by echocardiography, mouse hearts were harvested and cardiac resident CCR2- macrophages were sorted, followed by Smart sequencing. Bioinformatics analysis including GO, KEGG, and GSEA analyses were employed to elucidate transcriptional and functional changes.
Results:
Hyperlipidemia and obesity were observed easily upon HFD. The mouse hearts also displayed more severe fibrosis and diastolic dysfunction in HFD mice. Smart sequencing and functional analysis revealed metabolic dysfunctions, especially lipid-related genes and pathways. Besides this, antigen-presentation-related gene such as Ctsf and inflammation, particularly for NF-κB signaling and complement cascades, underwent drastic changes in cardiac resident macrophages. GO cellular compartment analysis was also performed and showed specific organelle enrichment trends of the involved genes.
Conclusion:
Dysregulated metabolism intertwines with inflammation in cardiac resident macrophages upon HFD feeding in mice, and further research on crosstalk among organelles could shed more light on potential mechanisms.
