药物抑制钠葡萄糖协同转运体 2 (SGLT2)已经成为治疗2型糖尿病（T2DM）、心血管疾病和/或其他代谢异常的方法，虽然其中一些有益影响的机制还不明确。SGLT2抑制剂(empagliflozin)被认为是脂肪组织、能量代谢和全身炎症的调节剂。我们的研究旨在评估6周empagliflozin治疗对糖尿病肥胖Zucker Diabetic Fatty (ZDF) 大鼠腹部(Visceral Adipose Tissue, VAT)和皮下脂肪(Subcutaneous Adipose Tissue, SAT)脂质组的影响,采用无靶向代谢组学方法。我们发现empagliflozin增加了VAT内二甘酰基甘油和氧化脂肪酸的含量，而在SAT中降低了一些溶血磷脂酰肌醇和增加了2个磷酰胆碱的水平。Empagliflozin还减少了VAT细胞因子白细胞介素-1 beta (IL-1β)，IL-6，肿瘤坏死因子α (TNF-α)，单核细胞趋化蛋白-1 (MCP-1)和IL-10的表达，以及Cd86和Cd163 M1和M2巨噬细胞标志物，但在SAT中没有变化，除了IL-1β的下降。Empagliflozin治疗还对脂肪分解产生影响，增加了SAT和VAT中激素敏感性脂肪酶的表达，以及VAT中脂肪三酰酶的表达，伴随着脂肪酸转运体分化群36 (CD36)的脂肪含量的降低。总之，我们的数据突出了VAT和SAT的脂质组、炎症谱和脂解功能上的差异，表明经empagliflozin治疗后这两种白色脂肪组织成分的代谢有所不同。 Copyright © 2023. Published by Elsevier Masson SAS.

The pharmacological inhibition of sodium-glucose cotransporter 2 (SGLT2) has emerged as a treatment for patients with type 2 diabetes mellitus (T2DM), cardiovascular disease and/or other metabolic disturbances, although some of the mechanisms implicated in their beneficial effects are unknown. The SGLT2 inhibitor (SGLT2i) empagliflozin has been suggested as a regulator of adiposity, energy metabolism, and systemic inflammation in adipose tissue. The aim of our study was to evaluate the impact of a 6-week-empagliflozin treatment on the lipidome of visceral (VAT) and subcutaneous adipose tissue (SAT) from diabetic obese Zucker Diabetic Fatty (ZDF) rats using an untargeted metabolomics approach. We found that empagliflozin increases the content of diglycerides and oxidized fatty acids (FA) in VAT, while in SAT, it decreases the levels of several lysophospholipids and increases 2 phosphatidylcholines. Empagliflozin also reduces the expression of the cytokines interleukin-1 beta (IL-1β), IL-6, tumor necrosis factor-alpha (TNFα), monocyte-chemotactic protein-1 (MCP-1) and IL-10, and of Cd86 and Cd163 M1 and M2 macrophage markers in VAT, with no changes in SAT, except for a decrease in IL-1β. Empagliflozin treatment also shows an effect on lipolysis increasing the expression of hormone-sensitive lipase (HSL) in SAT and VAT and of adipose triglyceride lipase (ATGL) in VAT, together with a decrease in the adipose content of the FA transporter cluster of differentiation 36 (CD36). In conclusion, our data highlighted differences in the VAT and SAT lipidomes, inflammatory profiles and lipolytic function, which suggest a distinct metabolism of these two white adipose tissue depots after the empagliflozin treatment.Copyright © 2023. Published by Elsevier Masson SAS.