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Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
c-MAF-dependent perivascular macrophages regulate diet-induced metabolic syndrome
Hernandez Moura Silva1, Jamil Zola Kitoko1,2, Camila Pereira Queiroz1,3
1Kimmel Center for Biology and Medicine at the Skirball Institute; New York University School of Medicine, New York, NY 10016, USA.
Abstract:
Macrophages are an essential part of tissue development and physiology. Perivascular macrophages have been described in tissues and appear to play a role in development and disease processes, although it remains unclear what the key features of these cells are. Here, we identify a subpopulation of perivascular macrophages in several organs, characterized by their dependence on the transcription factor c-MAF and displaying nonconventional macrophage markers including LYVE1, folate receptor 2, and CD38. Conditional deletion of c-MAF in macrophage lineages caused ablation of perivascular macrophages in the brain and altered muscularis macrophages program in the intestine. In the white adipose tissue (WAT), c-MAF–deficient perivascular macrophages displayed an altered gene expression profile, which was linked to an increased vascular branching. Upon feeding high-fat diet (HFD), mice with c-MAF–deficient macrophages showed improved metabolic parameters compared with wild-type mice, including less weight gain, greater glucose tolerance, and reduced inflammatory cell profile in WAT. These results define c-MAF as a central regulator of the perivascular macrophage transcriptional program in vivo and reveal an important role for this tissue-resident macrophage population in the regulation of metabolic syndrome.
Insights
This study identifies a specific type of perivascular macrophage regulated by the c-MAF transcription factor. These macrophages play a key role in metabolic syndrome, with their absence improving metabolic health in mice on a high-fat diet.
Area of Science:
- Immunology
- Cell Biology
- Metabolic Research
Background:
- Perivascular macrophages are crucial for tissue homeostasis and disease.
- Their specific characteristics and regulatory mechanisms remain largely undefined.
Purpose of the Study:
- To identify and characterize a distinct subpopulation of perivascular macrophages.
- To investigate the role of the transcription factor c-MAF in regulating these macrophages.
- To explore the impact of c-MAF–dependent perivascular macrophages on metabolic syndrome.
Main Methods:
- Identification of perivascular macrophage subpopulations using specific markers (LYVE1, folate receptor 2, CD38).
- Conditional deletion of the c-MAF gene in macrophage lineages.
- Analysis of gene expression profiles in white adipose tissue (WAT).
- Assessment of metabolic parameters in mice fed a high-fat diet (HFD).
Main Results:
- A c-MAF–dependent subpopulation of perivascular macrophages was identified across multiple organs.
- Conditional deletion of c-MAF led to the ablation of brain perivascular macrophages and altered intestinal muscularis macrophages.
- In WAT, c-MAF deficiency resulted in altered gene expression and increased vascular branching.
- Mice with c-MAF–deficient macrophages exhibited improved metabolic parameters, including reduced weight gain and better glucose tolerance, upon HFD feeding.
Conclusions:
- c-MAF is a central regulator of the perivascular macrophage transcriptional program in vivo.
- Perivascular macrophages are critical regulators of metabolic syndrome.
- Targeting c-MAF–dependent perivascular macrophages may offer therapeutic strategies for metabolic disorders.

