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

Shih-Jie Jhuo1,2, I-Hsin Liu1, Wei-Chung Tsai1,2,3

  • 1Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan.

Molecules (Basel, Switzerland)
|August 14, 2020
PubMed

Insights

Empagliflozin (EMPA) therapy may prevent cardiac arrhythmias by modulating pericardial fat adipocytokines. EMPA improved potassium and calcium channel currents in cardiomyocytes, unlike peripheral fat effects.

Area of Science:

  • Cardiology
  • Endocrinology
  • Pharmacology

Background:

  • Sodium-glucose transporter 2 (SGLT2) inhibitors, like empagliflozin (EMPA), reduce cardiovascular mortality.
  • The anti-arrhythmic effects of EMPA, particularly concerning cardiac ion channel function, remain unclear.
  • Metabolic syndrome (MS) is associated with altered adipocytokine profiles and cardiovascular complications.

Purpose of the Study:

  • To investigate the effects of empagliflozin (EMPA) on cardiac ion channel function in a mouse model of metabolic syndrome (MS).
  • To determine whether EMPA influences adipocytokines from pericardial and peripheral fat and their impact on cardiomyocyte ion currents.
  • To elucidate potential anti-arrhythmic mechanisms of SGLT2 inhibitors.

Main Methods:

  • Establishment of a metabolic syndrome (MS) mouse model using a high-fat diet.
  • Treatment groups included control, MS, MS + EMPA, and MS + glibenclamide (GLI).
  • Measurement of delayed-rectifier potassium current (IK) and L-type calcium channel current (ICa,L) using whole-cell patch clamp after exposing H9c2 cells to adipocytokines.

Main Results:

  • Adipocytokines from MS mice's pericardial fat decreased IK and increased ICa,L in cardiomyocytes.
  • EMPA and GLI treatments significantly restored IK and reduced ICa,L when using pericardial fat adipocytokines.
  • EMPA demonstrated a superior effect on restoring IK compared to GLI; peripheral fat adipocytokines showed no significant effects.

Conclusions:

  • Empagliflozin (EMPA) therapy, via pericardial fat adipocytokines, attenuates MS-induced alterations in cardiomyocyte ion currents.
  • These findings suggest EMPA may exert anti-arrhythmic effects by modulating pericardial adipocytokine signaling.
  • The study highlights a potential mechanism for SGLT2 inhibitors in managing cardiac arrhythmias associated with metabolic dysfunction.
Keywords:
adipocytokinedelayed-rectifier potassium currentl-type calcium channel currentpericardial fat

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