WWP1 localizes in the Golgi apparatus and contributes to maintaining glycosaminoglycan synthesis in adipocytes

Abstract

White adipocytes are a major component of white adipose tissue (WAT) and help to maintain systemic metabolic homeostasis because they store energy and secrete adipokines. In mice deficient in the protein WWP1 (WW domain-containing E3 ubiquitin protein ligase 1) oxidative stress in adipocytes is increased but insulin resistance induced by obesity is improved. However, the specific roles of WWP1 in adipocytes remain unclear. Here, we show that in 3T3L1 adipocytes WWP1 is localized in the Golgi apparatus and can protect the Golgi apparatus from monensin-induced disruption. By contrast, WWP1 knockdown by short hairpin RNA not only failed to protect the Golgi apparatus but also enhanced Golgi apparatus disruption by monensin. The Golgi apparatus acts as a central organelle to establish accurate protein glycosylation of proteoglycans containing glycosaminoglycans, including chondroitin sulfate (CS) and heparan sulfate (HS). Thus, we measured the amount of CS and HS and found that WWP1 overexpression increased CS and HS levels, whereas WWP1 knockdown decreased them. Furthermore, obesity-related increases in HS were prevented by WWP1 knockout in adipose tissue. In summary, we show that WWP1 in adipocytes localizes to the Golgi apparatus and may protect Golgi apparatus structure by contributing to the synthesis of proteoglycans.