Effects of secretome from fat tissues on ion currents of cardiomyocyte modulated by sodium-glucose transporter 2 inhibitor

Abstract

Sodium-glucose transporter 2 (SGLT2) inhibitors were shown to decrease mortality from cardiovascular diseases in the EMPA-REG trial. However, the effects of empagliflozin (EMPA) for cardiac arrhythmia are not yet clarified. A total of 20 C57BL/6J mice were divided into four groups: (1) The control group were fed standard chow, (2) the metabolic syndrome (MS) group were fed a high-fat diet, (3) the empagliflozin (EMPA) group were fed a high-fat diet and empagliflozin 10 mg/kg daily, and (4) the glibenclamide (GLI) group were fed a high-fat diet and glibenclamide 0.6 mg/kg daily. All mice were sacrificed after 16 weeks of feeding. H9c2 cells were treated with adipocytokines from the pericardial and peripheral fat from the study groups. The delayed-rectifier potassium current (IK) and L-type calcium channel current (ICa,L) were measured by the whole-cell patch clamp techniques. Adipocytokines from the peripheral and pericardial fat tissues of mice with MS could decrease the IK and increase the ICa,L of cardiomyocytes. After treating adipocytokines from pericardial fat, the IK in the EMPA and GLI groups were significantly higher than that in the MS group. The IK of the EMPA group was also significantly higher than the GLI group. The ICa,L of the EMPA and GLI groups were significantly decreased overload compared with that of the MS group. However, there was no significant difference of IK and ICa,L among study groups after treating adipocytokines from peripheral fat. Adipocytokines from pericardial fat but not peripheral fat tissues after EMPA therapy attenuated the effects of IK decreasing and ICa,L increasing in the MS cardiomyocytes, which may contribute to anti-arrhythmic mechanisms of sodium-glucose transporter 2 (SGLT2) inhibitors.