Empagliflozin does not reverse lipotoxicity-induced impairment in human myeloid angiogenic cell bioenergetics

• DOI: 10.1186/s12933-022-01461-4
• Publication Date: 2022-02-17T12:06:09Z
• Authors: Gloria Cinquegrani; Valentina Spigoni; Federica Fantuzzi; Riccardo C. Bonad...; Alessandra Dei Cas
• Keywords: Lipotoxicity; Empagliflozin; Bioenergetics

Abstract Background Empagliflozin can curb inflammation and oxidative stress, through sodium-proton exchanger (NHE) inhibition, in a model of lipotoxicity human myeloid angiogenic cells (MAC), which mediate endothelial repairing processes. Aim this study is to assess MAC whether: (1) Stearic acid (SA) induced increase oxidant stress accompanied by bioenergetic alterations; (2) empagliflozin anti-lipotoxic action concomitant with coherent changes metabolism, possibly via NHE blockade. Methods were isolated from peripheral blood healthy volunteers incubated the presence/absence SA (100 μM for 3 h) with/without (EMPA 100 μM) or amiloride (Ami 1 h. Cell respiration (oxygen consumption rate OCR) anaerobic glycolysis (measured as proton production rate) recorded real-time Seahorse technology, ATP (anaerobic glycolysis- oxphos-derived) rates calculated. Results SA, at concentration causing increased altered cell bioenergetics MAC, overall reductions basal OCR oxphos-derived (all p < 0.05), pointing mitochondrial alterations. EMPA, counteracting SA-induced lipotoxicity, both alone presence caused NHE-independent extensive alterations (from 0.05 0.01), greater than those alone. Conclusions In MAC: bioenergetics, concomitantly stress; EMPA inhibited respiration, (3) protective effect against was unlikely be mediated metabolism.