Effects of Secretome from Fat Tissues on Ion Currents of Cardiomyocyte Modulated by Sodium-Glucose Transporter 2 Inhibitor

• Main Authors: Shih-Jie Jhuo, I-Hsin Liu, Wei-Chung Tsai, Te-Wu Chou, Yi-Hsiung Lin, Bin-Nan Wu, Kun-Tai Lee, Wen-Ter Lai
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: Molecules
• Subjects: pericardial fat; adipocytokine; delayed-rectifier potassium current; <span style="font-variant: small-caps">l</span>-type calcium channel current
• Online Access: https://www.mdpi.com/1420-3049/25/16/3606

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 (I_K) and L-type calcium channel current (I_Ca,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 I_K and increase the I_Ca,L of cardiomyocytes. After treating adipocytokines from pericardial fat, the I_K in the EMPA and GLI groups were significantly higher than that in the MS group. The I_K of the EMPA group was also significantly higher than the GLI group. The I_Ca,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 I_K and I_Ca,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 I_K decreasing and I_Ca,L increasing in the MS cardiomyocytes, which may contribute to anti-arrhythmic mechanisms of sodium-glucose transporter 2 (SGLT2) inhibitors.