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.

Science Immunology
|October 1, 2021
PubMed

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.

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