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

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 16; p. 3606
• Main Authors: Jhuo, Shih-Jie, Liu, I-Hsin, Tsai, Wei-Chung, Chou, Te-Wu, Lin, Yi-Hsiung, Wu, Bin-Nan, Lee, Kun-Tai, Lai, Wen-Ter
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 08.08.2020; MDPI
• Subjects: adipocytokine; Adipokines - metabolism; Adipose Tissue - drug effects; Adipose Tissue - metabolism; Animal tissues; Animals; Arrhythmia; Benzhydryl Compounds - pharmacology; Body Weight - drug effects; Calcium; Calcium channels (L-type); Cardiac arrhythmia; Cardiomyocytes; Cardiovascular disease; Cardiovascular diseases; Cell Line; Cytokines; delayed-rectifier potassium current; Diabetes; Glibenclamide; Glucose; Glucose transporter; Glucosides - pharmacology; Heart failure; High fat diet; Humans; Inhibitors; Ion currents; l -type calcium channel current; Metabolic disorders; Metabolic syndrome; Metabolism; Metabolites; Mice; Mice, Inbred C57BL; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; pericardial fat; Potassium; Secretome; Sodium; Sodium-Glucose Transporter 2 Inhibitors - pharmacology; Studies; Tumor necrosis factor-TNF; adipocytokine; l-type calcium channel current; delayed-rectifier potassium current; pericardial fat
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25163606

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