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

Empagliflozin does not reverse lipotoxicity-induced impairment in human myeloid angiogenic cell bioenergetics / Cinquegrani, G.; Spigoni, V.; Fantuzzi, F.; Bonadonna, R. C.; Dei Cas, A.. - In: CARDIOVASCULAR DIABETOLOGY. - ISSN 1475-2840. - 21:1(2022), p. 27.27. [10.1186/s12933-022-01461-4]

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

Cinquegrani G.;Spigoni V.;Fantuzzi F.;Bonadonna R. C.
;
Dei Cas A.
2022

Abstract

Background: Empagliflozin can curb inflammation and oxidative stress, through sodium-proton exchanger (NHE) inhibition, in a model of lipotoxicity in human myeloid angiogenic cells (MAC), which mediate endothelial repairing processes. Aim of this study is to assess in human MAC whether: (1) Stearic acid (SA) induced inflammation and increase in oxidant stress is accompanied by bioenergetic alterations; (2) empagliflozin anti-lipotoxic action is concomitant with coherent changes in bioenergetic metabolism, possibly via NHE blockade. Methods: MAC were isolated from peripheral blood of healthy volunteers and incubated in the presence/absence of SA (100 μM for 3 h) with/without empagliflozin (EMPA 100 μM) or amiloride (Ami 100 μM) for 1 h. Cell respiration (oxygen consumption rate OCR) and anaerobic glycolysis (measured as proton production rate) were recorded in real-time by Seahorse technology, and ATP production (anaerobic glycolysis- and oxphos-derived) rates were calculated. Results: SA, at the concentration causing inflammation and increased oxidant stress, altered cell bioenergetics of human MAC, with overall reductions in basal OCR and oxphos-derived ATP production (all p < 0.05), pointing to mitochondrial alterations. EMPA, at the concentration counteracting SA-induced lipotoxicity, both alone and in the presence of SA, caused NHE-independent extensive bioenergetic alterations (from p < 0.05 to p < 0.01), greater than those induced by SA alone. Conclusions: In human MAC: (1) SA altered cell bioenergetics, concomitantly with inflammation and oxidant stress; (2) EMPA possibly inhibited mitochondrial respiration, (3) the protective effect of EMPA against SA-induced lipotoxicity was unlikely to be mediated through bioenergetic metabolism.
Empagliflozin does not reverse lipotoxicity-induced impairment in human myeloid angiogenic cell bioenergetics / Cinquegrani, G.; Spigoni, V.; Fantuzzi, F.; Bonadonna, R. C.; Dei Cas, A.. - In: CARDIOVASCULAR DIABETOLOGY. - ISSN 1475-2840. - 21:1(2022), p. 27.27. [10.1186/s12933-022-01461-4]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2918323
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