Editors' ChoiceWound Healing

Fat cells help wounds heal

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Science Signaling  07 Jul 2020:
Vol. 13, Issue 639, eabd6235
DOI: 10.1126/scisignal.abd6235

Dermal adipocytes promote wound healing by recruiting macrophages and transdifferentiating into myofibroblasts.

Wound healing requires precise coordination of the activities of epithelia, fibroblasts, and macrophages, but other cell types are increasingly appreciated to contribute. Dermal adipocytes, which are functionally distinct from adipocytes in subcutaneous adipose tissue, participate in wound repair and other processes in the skin. Shook et al. found that depleting dermal adipocytes before skin wounding reduced macrophage recruitment to the wound and delayed revascularization and re-epithelialization of the wound bed. In normal skin, the lipid content of adipocytes at the wound edge decreased as macrophages were recruited to the wound. Inducible knockout of adipose triglyceride lipase (ATGL) specifically in dermal adipocytes to block lipolysis prevented this reduction in lipid content, reduced the amounts of several fatty acids in the wound bed, impaired macrophage recruitment, and delayed revascularization. Lineage tracing experiments showed that adipocytes at wound edges lost adipocyte-specific markers and migrated into wound beds after reducing their lipid content but did not migrate into wound beds when lipolysis was blocked. Transcriptomic profiling of lineage-traced adipocytes that migrated into the wound bed showed that they expressed markers of activated fibroblasts (myofibroblasts), which are contractile cells that contribute to wound healing by modifying the extracellular matrix and secreting growth factors that drive repair. Thus, adipocytes at wound sites migrate into the wound bed and transdifferentiate into myofibroblasts after dedifferentiating, undergoing lipolysis, and releasing fatty acids, including two that stimulate macrophage activation (see commentary by Merrick and Seale), into the wound bed. Whether and how the fatty acids released by dermal adipocytes contribute to macrophage recruitment has yet to be determined.

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