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Empagliflozin does not reverse lipotoxicity-induced impairment in human myeloid angiogenic cell bioenergetics
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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8851739/ https://www.ncbi.nlm.nih.gov/pubmed/35177077 http://dx.doi.org/10.1186/s12933-022-01461-4 |
Sumario: | 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. |
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