BMP4 facilitates beige fat biogenesis via regulating adipose tissue macrophages

J Mol Cell Biol. 2019 Jan 1;11(1):14-25. doi: 10.1093/jmcb/mjy011.

Abstract

Thermogenic beige fat improves metabolism and prevents obesity. Emerging evidence shows that the activation of M2 macrophages stimulates beige adipogenesis, whereas the activation of M1 macrophages, which play a major role in inflammation, impedes beige adipogenesis. Thus, the identification of factors that regulate adipose tissue macrophages (ATMs) will help clarify the mechanism involved in beiging. Here, we found that one of the secreted proteins in adipose tissue, namely, BMP4, alters the ATM profile in subcutaneous adipose tissue by activating M2 and inhibiting M1 macrophages. Mechanistically, the BMP4-stimulated p38/MAPK/STAT6/PI3K-AKT signalling pathway is involved. Meanwhile, BMP4 improved the potency of M2 macrophages to induce beige fat biogenesis. Considering that the overexpression of BMP4 in adipose tissue promotes the beiging of subcutaneous adipose tissue and improves insulin sensitivity, these findings provide evidence that BMP4 acts as an activator of beige fat by targeting immuno-metabolic pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue, Beige / metabolism*
  • Animals
  • Bone Morphogenetic Protein 4 / genetics
  • Bone Morphogenetic Protein 4 / metabolism*
  • Bone Morphogenetic Protein 4 / pharmacology
  • Cell Proliferation
  • Cytokines / genetics
  • Cytokines / metabolism
  • Insulin Resistance
  • Lipopolysaccharides / pharmacology
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinases / metabolism
  • Obesity / metabolism
  • Obesity / pathology
  • Phosphatidylinositol 3-Kinases / metabolism
  • STAT6 Transcription Factor / metabolism
  • Signal Transduction
  • Subcutaneous Fat / metabolism

Substances

  • Bmp4 protein, mouse
  • Bone Morphogenetic Protein 4
  • Cytokines
  • Lipopolysaccharides
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Mitogen-Activated Protein Kinases