부산대학교 도서관

Aims In patients with cardiovascular disease, epicardial adipose tissue (EAT) is characterized by insulin resistance, highpro-inflammatory chemokines, and low differentiation ability As dapagliflozin reduces body fat and cardiovascularevents in diabetic patients, we would like to know its effect on EAT and subcutaneous adipose tissue (SAT)Methodsand resultsAdipose samples were obtained from 52 patients undergoing heart surgery Sodium-glucose cotransporter 2(SGLT2) expression was determined by real-time polymerase chain reaction (n = 20), western blot, and immunohistochemistryFat explants (n = 21) were treated with dapagliflozin and/or insulin and glucose transporters expressionmeasured Glucose, free fatty acid, and adipokine levels (by array) were measured in the EAT secretomes, whichwere then tested on human coronary endothelial cells using wound healing assays Glucose uptake was also measuredusing the fluorescent glucose analogue (6NBDG) in differentiated stromal vascular cells (SVCs) from the fatpads (n = 11) Finally, dapagliflozin-induced adipocyte differentiation was assessed from the levels of fat droplets(AdipoRed staining) and of perilipin SGLT2 was expressed in EAT Dapagliflozin increased glucose uptake(2095 ± 44 mg/dL vs 1297 ± 41 mg/dL; P < 0001) and glucose transporter type 4 (209 ± 03 fold change; P < 001)in EAT Moreover, dapagliflozin reduced the secretion levels of chemokines and benefited wound healing in endothelialcells (021 ± 005 vs 038 ± 008 open wound; P < 005) Finally, chronic treatment with dapagliflozin improvedthe differentiation of SVC, confirmed by AdipoRed staining [539 ± 142 arbitrary units (au) vs 473 ± 136 au;P < 001] and perilipin expression levels (121 ± 10 vs 84 ± 11 au)Conclusions Dapagliflozin increased glucose uptake, reduced the secretion of pro-inflammatory chemokines (with a beneficialeffect on the healing of human coronary artery endothelial cells), and improved the differentiation of EAT cellsThese results suggest a new protective pathway for this drug on EAT from patients with cardiovascular disease [ABSTRACT FROM AUTHOR]