CD81 Controls Beige Fat Progenitor Cell Growth and Energy Balance via FAK Signaling

Yasuo Oguri, Kosaku Shinoda, Hyeonwoo Kim, Diana L. Alba, W. Reid Bolus, Qiang Wang, Zachary Brown, Rachana N. Pradhan, Kazuki Tajima, Takeshi Yoneshiro, Kenji Ikeda, Yong Chen, Rachel T. Cheang, Kazuyuki Tsujino, Caroline R. Kim, Vanille Juliette Greiner, Ritwik Datta, Christopher D. Yang, Kamran Atabai, Michael T. McManusSuneil K. Koliwad, Bruce M. Spiegelman, Shingo Kajimura

Research output: Contribution to journalArticlepeer-review

139 Scopus citations


Adipose tissues dynamically remodel their cellular composition in response to external cues by stimulating beige adipocyte biogenesis; however, the developmental origin and pathways regulating this process remain insufficiently understood owing to adipose tissue heterogeneity. Here, we employed single-cell RNA-seq and identified a unique subset of adipocyte progenitor cells (APCs) that possessed the cell-intrinsic plasticity to give rise to beige fat. This beige APC population is proliferative and marked by cell-surface proteins, including PDGFRα, Sca1, and CD81. Notably, CD81 is not only a beige APC marker but also required for de novo beige fat biogenesis following cold exposure. CD81 forms a complex with αV/β1 and αV/β5 integrins and mediates the activation of integrin-FAK signaling in response to irisin. Importantly, CD81 loss causes diet-induced obesity, insulin resistance, and adipose tissue inflammation. These results suggest that CD81 functions as a key sensor of external inputs and controls beige APC proliferation and whole-body energy homeostasis.

Original languageEnglish (US)
Pages (from-to)563-577.e20
Issue number3
StatePublished - Aug 6 2020


  • adipocyte progenitors
  • adipogenesis
  • beige fat
  • brown fat
  • diabetes
  • metabolic adaptation
  • metabolic disease
  • metabolism
  • obesity
  • tissue remodeling

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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