Adipocyte lipolysis activates epithelial stem cells for hair regeneration through fatty acid metabolic signaling.
Journal
Cell metabolism
Journal Volume
37
Journal Issue
11
Start Page
2202
End Page
2219.e8
ISSN
1932-7420
Date Issued
2025-11-04
Author(s)
Tai, Kang-Yu
Chen, Chih-Lung
Fan, Sabrina Mai-Yi
Lin, Chun-Kai
Huang, Hsin-Wen
Lee, Hao-Wei
Wang, Shiou-Han
Chang, Nai-Wen
Plikus, Maksim V
Abstract
Adipocytes as vital energy reservoirs respond to systemic metabolic demands by storing or releasing lipids. Whether they can promote tissue regeneration through local metabolic communication remains unclear. We found that after skin injury, macrophages quickly infiltrate dermal adipose tissue, where they promote free fatty acid release from adipocytes via serum amyloid A3-dependent lipolysis, which, in turn, promotes hair regrowth. Epithelial hair follicle stem cells (eHFSCs) absorb the released monounsaturated fatty acids via fatty acid translocase CD36 and activate the transcriptional coactivator Pgc1-α. Downstream of Pgc1-α, increased fatty acid oxidation and mitochondrial biogenesis enhance energy production, enabling eHFSCs to exit quiescence. Topical treatment of monounsaturated fatty acids suffices to promote hair growth by activating eHFSCs. Our findings demonstrate a macrophage-to-adipocyte-to-hair follicle axis that promotes tissue-level regeneration via short-range metabolic signaling through free fatty acids. Analogous regeneration-facilitating mechanisms elicited by injury-induced panniculitis may operate in other adipose-rich organs.
Subjects
adipocyte
fatty acid oxidation
hair follicle
inflammation
lipolysis
macrophage
mitochondrial biogenesis
panniculitis
serum amyloid A3
tissue regeneration
Publisher
Cell Press
Type
journal article