High released lactate by epicardial fat from coronary artery disease patients is reduced by dapagliflozin treatment.

Autor: Couselo-Seijas M; Translational Cardiology Group, Health Research Institute of Santiago de Compostela, Spain., Agra-Bermejo RM; Cardiovascular Area and Coronary Unit, University Clinical Hospital of Santiago de Compostela, Spain; CIBERCV, Madrid, Spain; Cardiology Group, Health Research Institute of Santiago de Compostela, Spain., Fernández AL; CIBERCV, Madrid, Spain; Heart Surgery Department University Clinical Hospital of Santiago de Compostela, Spain., Martínez-Cereijo JM; Heart Surgery Department University Clinical Hospital of Santiago de Compostela, Spain., Sierra J; Heart Surgery Department University Clinical Hospital of Santiago de Compostela, Spain., Soto-Pérez M; Cardiovascular Area and Coronary Unit, University Clinical Hospital of Santiago de Compostela, Spain., Rozados-Luis A; Translational Cardiology Group, Health Research Institute of Santiago de Compostela, Spain., González-Juanatey JR; Cardiovascular Area and Coronary Unit, University Clinical Hospital of Santiago de Compostela, Spain; CIBERCV, Madrid, Spain; Cardiology Group, Health Research Institute of Santiago de Compostela, Spain., Eiras S; Translational Cardiology Group, Health Research Institute of Santiago de Compostela, Spain; CIBERCV, Madrid, Spain. Electronic address: sonia.eiras.penas@sergas.es.
Jazyk: angličtina
Zdroj: Atherosclerosis [Atherosclerosis] 2020 Jan; Vol. 292, pp. 60-69. Date of Electronic Publication: 2019 Nov 15.
DOI: 10.1016/j.atherosclerosis.2019.11.016
Abstrakt: Background and Aims: Dapagliflozin, a sodium-glucose co-transporter 2 inhibitor, improves glucose uptake by epicardial adipose tissue (EAT). However, its metabolism might raise the lactate production and acidosis under hypoxia conditions, i.e. coronary artery disease (CAD), or lipogenesis and, in consequence, expand adipose tissue. Since lactate secreted by adipose tissue is correlated with tissue stress and inflammation, our aim was to study glucose metabolism by epicardial fat in CAD and its regulation by dapagliflozin.
Methods: Paired EAT and subcutaneous adipose tissue (SAT) biopsies from 49 patients who underwent open-heart surgery were cultured and split into three equal pieces, some treated with and others without dapagliflozin at 10 or 100 μM for 6 h. Anaerobic glucose metabolites were measured in supernatants of fat pads, and acidosis on adipogenesis-induced primary culture cells was analysed by colorimetric or fluorescence assays. Gene expression levels were assessed by real-time polymerase chain reaction.
Results: Our results showed that dapagliflozin reduced the released lactate and acidosis in epicardial fat (p < 0.05) without changes in lipid storage-involved genes. In addition, this drug induced gene expression levels of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α), a mitochondrial biogenesis-involved gene in both EAT and SAT (p < 0.05). After splitting the population regarding the presence of CAD, we observed higher lactate production in EAT from these patients (2.46 [1.75-3.47] mM), which was reduced after treatment with dapagliflozin 100 μM (1.99 [1.08-2.99] mM, p < 0.01).
Conclusions: Dapagliflozin improved glucose metabolism without lipogenesis-involved gene regulation or lactate production, mainly in patients with CAD. These results suggest an improvement of glucose oxidation metabolism that can contribute to cardiovascular benefits.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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