The browning and mobilization of subcutaneous white adipose tissue supports efficient skin repair

Cell Metab. 2024 Jun 4;36(6):1287-1301.e7. doi: 10.1016/j.cmet.2024.05.005.

Abstract

Adipocytes in dermis are considered to be important participants in skin repair and regeneration, but the role of subcutaneous white adipose tissue (sWAT) in skin repair is poorly understood. Here, we revealed the dynamic changes of sWAT during wound healing process. Lineage-tracing mouse studies revealed that sWAT would enter into the large wound bed and participate in the formation of granulation tissue. Moreover, sWAT undergoes beiging after skin injury. Inhibition of sWAT beiging by genetically silencing PRDM16, a key regulator to beiging, hindered wound healing process. The transcriptomics results suggested that beige adipocytes in sWAT abundantly express neuregulin 4 (NRG4), which regulated macrophage polarization and the function of myofibroblasts. In diabetic wounds, the beiging of sWAT was significantly suppressed. Thus, adipocytes from sWAT regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes.

Keywords: adipocyte browning; cellular plasticity; neuregulin 4; subcutaneous adipose tissue; wound healing.

MeSH terms

  • Adipocytes, Beige / metabolism
  • Adipose Tissue, Brown / metabolism
  • Adipose Tissue, White* / metabolism
  • Animals
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Humans
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Myofibroblasts / metabolism
  • Neuregulins / genetics
  • Neuregulins / metabolism
  • Skin* / metabolism
  • Skin* / pathology
  • Subcutaneous Fat / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Wound Healing*

Substances

  • neuregulin-4
  • Transcription Factors
  • Prdm16 protein, mouse
  • Neuregulins
  • DNA-Binding Proteins