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

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 adipocytes from sWAT would migrate into the 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 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. Overall design: Inguinal subcutaneous white adipose tissue (sWAT) samples collected from C57BL/6 mice 7 days after skin injury and uninjured mice (n = 3 per group) were used to characterize the transcriptome of sWAT following injury. We also collected the sWAT beneath the wounds of Adipo-PRDM16 KO and C57BL/6 mice (n = 3 per group) 7 days after skin injury to characterize the transcriptome of sWAT after the inhibition of browning.