High released lactate by epicardial fat from coronary artery disease patients is reduced by dapagliflozin treatment
Autor: | Marinela Couselo-Seijas, Juan Sierra, Sonia Eiras, Rosa Agra-Bermejo, Maeve Soto-Pérez, Adriana Rozados-Luis, José Ramón González-Juanatey, Ángel L. Fernández, J M Martinez-Cereijo |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
medicine.medical_specialty Glucose uptake Adipose tissue Coronary Artery Disease 030204 cardiovascular system & hematology Carbohydrate metabolism Sodium-Glucose Transport Proteins 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Glucosides Internal medicine Medicine Humans Lactic Acid Dapagliflozin Benzhydryl Compounds Acidosis business.industry 030104 developmental biology Endocrinology Glucose chemistry Adipose Tissue Lipogenesis medicine.symptom SGLT2 Inhibitor Cardiology and Cardiovascular Medicine business Anaerobic exercise Pericardium |
Zdroj: | Atherosclerosis. 292 |
ISSN: | 1879-1484 |
Popis: | 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.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.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).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. |
Databáze: | OpenAIRE |
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