A potent soluble epoxide hydrolase inhibitor, t-AUCB, modulates cholesterol balance and oxidized low density lipoprotein metabolism in adipocytes in vitro

作者：Shen, Li; Peng, Hongchun; Zhao, Shuiping; Xu, Danyan^*

来源：Biological Chemistry, 2014, 395(4): 443-451.

DOI：10.1515/hsz-2013-0251

• adipocytokine
• cholesterol efflux
• epoxyeicosatrienoic acids
• oxLDL
• soluble epoxide hydrolase

The cholesterol metabolism in adipose tissue is dependent on the balance between cholesterol uptake and efflux. Adipocytes dysfunction and its cholesterol imbalance are associated with obesity. Adipocytes are the site for clearance of oxidized low density lipoprotein (oxLDL) in blood. Soluble epoxide hydrolase (sEH) is highly expressed in adipocytes. sEH converts epoxyeicosatrienoic acids (EETs) into less bioactive dihydroxyeicosatrienoic acids, which regulate cholesterol metabolism in adipocytes and block the development of atherosclerosis. In vitro, 3T3-L1 differentiated adipocytes were incubated with the sEH inhibitor t-AUCB (0, 1, 10, 50 or 100 mu mol/l) for 24 h with or without the PPAR gamma inhibitor GW9662. To determine the effect of t-AUCB on oxLDL endocytosis, degradation and cholesterol efflux from adipocytes, we demonstrated that t-AUCB enhances the CD36-mediated recognition and degradation of oxLDL and improves cholesterol efflux via the upregulation of ABCA1 expression. Furthermore, t-AUCB blocked TNF-alpha secretion and increased adiponectin levels found in adipocytes culture medium. We provide evidence that these effects are PPAR gamma-dependent. These results suggest that an increase in EETs because of sEH inhibition could maintain cellular cholesterol homeostasis by the regulation of oxLDL clearance and cholesterol efflux via the EETs-PPAR gamma pathway.

• 出版日期2014-4
• 单位长沙市中心医院; 中南大学