An Hsp20-FBXO4 Axis Regulates Adipocyte Function through Modulating PPAR? Ubiquitination.

ABSTRACT: 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 (PPAR?). Indeed, Hsp20 deficiency mimics and enhances the pharmacological effects of the PPAR? agonist rosiglitazone. Together, our findings suggest a role of Hsp20 in mediating adipocyte function by linking ?-adrenergic signaling to PPAR? activity.

SUBMITTER: Peng J 

PROVIDER: S-EPMC6091893 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature