2. Academic Validation
  3. Adipocyte lipolysis activates epithelial stem cells for hair regeneration through fatty acid metabolic signaling

Adipocyte lipolysis activates epithelial stem cells for hair regeneration through fatty acid metabolic signaling

  • Cell Metab. 2025 Oct 22:S1550-4131(25)00397-3. doi: 10.1016/j.cmet.2025.09.012.
Kang-Yu Tai 1,  Chih-Lung Chen 2,  Sabrina Mai-Yi Fan 3,  Chen-Hsiang Kuan 4,  Chun-Kai Lin 2,  Hsin-Wen Huang 2,  Hao-Wei Lee 2,  Shiou-Han Wang 5,  Nai-Wen Chang 3,  Jian-Da Lin 6,  Che-Feng Chang 7,  Kai-Chien Yang 8,  Maksim V Plikus 9,  Sung-Jan Lin 10
Affiliations

Affiliations

  • 1 Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 106, Taiwan.
  • 2 Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 106, Taiwan.
  • 3 Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan.
  • 4 Division of Plastic Surgery, Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei 106, Taiwan.
  • 5 Department of Dermatology, National Taiwan University and National Taiwan University Hospital, Taipei 100, Taiwan.
  • 6 Department of Biochemical Science and Technology, National Taiwan University, Taipei 106, Taiwan; Center for Computational and Systems Biology, National Taiwan University, Taipei 106, Taiwan; Center for Advanced Computing and Imaging in Biomedicine, National Taiwan University, Taipei 106, Taiwan.
  • 7 Department and Graduate Institute of Physiology, National Taiwan University, Taipei 100, Taiwan.
  • 8 Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei 106, Taiwan; Department and Graduate Institute of Pharmacology, National Taiwan University, Taipei 100, Taiwan; Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
  • 9 Department of Developmental and Cell Biology, Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, Irvine, CA 92697, USA; Center for Complex Biological Systems, University of California, Irvine, Irvine, CA 92697, USA.
  • 10 Genome and Systems Biology Degree Program, National Taiwan University and Academia Sinica, Taipei 106, Taiwan; Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 106, Taiwan; Department of Medical Research, National Taiwan University Hospital, Taipei 100, Taiwan; Research Center for Developmental Biology and Regenerative Medicine, National Taiwan University, Taipei 106, Taiwan; Department of Dermatology, National Taiwan University and National Taiwan University Hospital, Taipei 100, Taiwan; Center for Computational and Systems Biology, National Taiwan University, Taipei 106, Taiwan; Genomics Research Center, Academia Sinica, Taipei 115, Taiwan. Electronic address: drsjlin@ntu.edu.tw.
PMID: 41130201 DOI: 10.1016/j.cmet.2025.09.012
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.

Keywords

adipocyte; fatty acid oxidation; hair follicle; inflammation; lipolysis; macrophage; mitochondrial biogenesis; panniculitis; serum amyloid A3; tissue regeneration.

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