Partial depletion of CD206-positive M2-like macrophages induces proliferation of beige progenitors and enhances browning after cold stimulation

Sci Rep. 2018 Oct 1;8(1):14567. doi: 10.1038/s41598-018-32803-6.

Abstract

Beige adipocytes are an inducible form of thermogenic adipocytes that become interspersed within white adipose tissue (WAT) depots in response to cold exposure. Previous studies have shown that type 2 cytokines and M2 macrophages induce cold-induced browning in inguinal WAT (ingWAT) by producing catecholamines. Exactly how the conditional and partial depletion of CD206+ M2-like macrophages regulates the cold-induced browning of ingWAT, however, remains unknown. We examined the role of CD206+ M2-like macrophages in the cold-induced browning of WAT using genetically engineered CD206DTR mice, in which CD206+ M2-like macrophages were conditionally depleted. The partial depletion of CD206+ M2-like enhanced UCP1 expression in ingWAT, as shown by immunostaining, and also upregulated the expression of Ucp1 and other browning-related marker genes in ingWAT after cold exposure. A flow cytometry analysis showed that the partial depletion of CD206+ M2-like macrophages caused an increase in the number of beige progenitors in ingWAT in response to cold. Thus, we concluded that CD206+ M2-like macrophages inhibit the proliferation of beige progenitors and that the partial depletion of CD206+ M2-like macrophages releases this inhibition, thereby enhancing browning and insulin sensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes, Beige / physiology*
  • Adipose Tissue / radiation effects*
  • Animals
  • Cell Proliferation*
  • Cold Temperature*
  • Flow Cytometry
  • Gene Expression Profiling
  • Lectins, C-Type / analysis*
  • Leukocyte Reduction Procedures*
  • Macrophages / chemistry
  • Macrophages / immunology*
  • Mannose Receptor
  • Mannose-Binding Lectins / analysis*
  • Mice
  • Receptors, Cell Surface / analysis*
  • Uncoupling Protein 1 / analysis

Substances

  • Lectins, C-Type
  • Mannose Receptor
  • Mannose-Binding Lectins
  • Receptors, Cell Surface
  • Ucp1 protein, mouse
  • Uncoupling Protein 1