An Hsp20-FBXO4 Axis Regulates Adipocyte Function through Modulating PPARγ Ubiquitination

Jiangtong Peng, Yutian Li, Xiaohong Wang, Shan Deng, Jenna Holland, Emily Yates, Jing Chen, Haitao Gu, Kobina Essandoh, Xingjiang Mu, Boyu Wang, Robert K. McNamara, Tianqing Peng, Anil G. Jegga, Tiemin Liu, Takahisa Nakamura, Kai Huang, Diego Perez-Tilve, Guo Chang Fan

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)


Exposure to cold temperature is well known to upregulate heat shock protein (Hsp) expression and recruit and/or activate brown adipose tissue and beige adipocytes in humans and animals. However, whether and how Hsps regulate adipocyte function for energy homeostatic responses is poorly understood. Here, we demonstrate a critical role of Hsp20 as a negative regulator of adipocyte function. Deletion of Hsp20 enhances non-shivering thermogenesis and suppresses inflammatory responses, leading to improvement of glucose and lipid metabolism under both chow diet and high-fat diet conditions. Mechanistically, Hsp20 controls adipocyte function by interacting with the subunit of the ubiquitin ligase complex, F-box only protein 4 (FBXO4), and regulating the ubiquitin-dependent degradation of peroxisome proliferation activated receptor gamma (PPARγ). Indeed, Hsp20 deficiency mimics and enhances the pharmacological effects of the PPARγ agonist rosiglitazone. Together, our findings suggest a role of Hsp20 in mediating adipocyte function by linking β-adrenergic signaling to PPARγ activity. Peng et al. identify a dual function for heat shock protein 20 (Hsp20) in regulating white adipocyte maturation and function through the FBXO4-PPARγ axis. The absence of Hsp20 improves the metabolic profile even under obesity conditions.

Original languageEnglish
Pages (from-to)3607-3620
Number of pages14
JournalCell Reports
Issue number12
Publication statusPublished - 2018 Jun 19


  • FBXO4
  • Hsp20
  • PPARγ
  • lipogenesis
  • thermogenesis
  • ubiquitination


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