Empagliflozin treatment differentially modifies visceral and subcutaneous adipose tissue lipidomes and pro-inflammatory cytokines in zucker fatty diabetic rats

Abstract EMPA-REG OUTCOME (Empagliflozin, Cardiovascular Outcome Event Trial) trial highlighted the relevance of pharmacological inhibition sodium-glucose cotransporter 2 (SGLT2) for treatment patients with type diabetes mellitus (T2DM) and/or cardiovascular disease. Although pathways through which SGLT2 inhibitors exert a beneficial effect on system are still unknown, it has been suggested that energy metabolism regulation and reduction systemic inflammation could be some mechanisms implicated. Available data also suggests empagliflozin able to regulatory effects adipose tissue (AT) depots. The aim our study was evaluate impact lipidome visceral (VAT) subcutaneous (SAT) depots in rat model obesity T2DM. Diabetic obese Zucker Fatty (ZDF) rats were treated 30 mg/kg/day p.o 6 weeks. lipidomes VAT SAT analyzed using ultra-high performance liquid chromatography coupled mass spectrometry. Empagliflozin's pro-inflammatory markers AT by RT-PCR. In VAT, 18 metabolites significantly altered empagliflozin-treated vs. controls. Nearly all diglycerides tested (13 14) increased rats, as most notable chemical class. Furthermore, 3 oxidized fatty acids (FA) FA like gadoleic acid linoleic increased. SAT, total 14 altered. Most them glycerophospholipids. Significantly lower levels 4 lysophosphatidylethanolamines, lysophosphatidylcholines, lysophosphatidylinositols higher phosphatidylcholines shown. contrast significant decrease these observed samples. Several ratios calculated infer potential enzyme activities related lipid both SAT. However, studied only statistically control, where main desaturases elongases. Empagliflozin reduces expression cytokines interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNFα) monocyte-chemotactic protein-1 (MCP-1) no changes except interleukin-13 (IL-13), decreases compared untreated diabetic ZDF rats. conclusion, decreased glycerophospholipid anti-inflammatory is not inflammatory profile different depending localization Funding Acknowledgement Type funding sources: Private company. Main source(s): Boehringer Ingelheim Pharma GmbH Co