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Sodium Glucose Cotransporter 2 (SGLT2) Inhibitor Ameliorate Metabolic Disorder and Obesity Induced Cardiomyocyte

Shih-Jie Jhuo1,2,3, Yi-Hsiung Lin2,4,5, I-Hsin Liu2

  • 1Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan.

International Journal of Molecular Sciences
|April 13, 2023
PubMed

Insights

Sodium-glucose transporter 2 inhibitors (SGLT2is) improve heart health by protecting cardiomyocyte mitochondria. Empagliflozin treatment reduced oxidative stress and calcium overload, enhancing mitochondrial function in metabolic disorder models.

Area of Science:

  • Cardiovascular Research
  • Metabolic Disorders
  • Mitochondrial Biology

Background:

  • Sodium-glucose transporter 2 inhibitors (SGLT2is) demonstrate cardiovascular and heart failure benefits in type 2 diabetes mellitus (DM).
  • The specific impact of SGLT2is on cardiomyocyte mitochondria remains incompletely understood.
  • Understanding these mechanisms is crucial for optimizing SGLT2i therapy in cardiovascular disease.

Purpose of the Study:

  • To investigate the effects of empagliflozin (EMPA) on cardiomyocyte mitochondrial function in a high-fat diet (HFD)-induced metabolic disorder and obesity (MDO) mouse model.
  • To elucidate the underlying mechanisms by which SGLT2is may exert cardioprotective effects at the mitochondrial level.
  • To compare the effects of EMPA with glibenclamide (GLI) in the MDO model.

Main Methods:

  • Mice were subjected to HFD for 16 weeks, with treatments including EMPA and GLI.
  • Epicardial fat secretomes were collected and used to treat H9c2 cells.
  • Mitochondrial reactive oxygen species (ROS) production, calcium (Ca2+) distribution, ATP production, and associated protein expression (SOD1, mfn2, SIRT1, SERCA) were analyzed.

Main Results:

  • EMPA treatment significantly reduced lipotoxicity, mitochondrial ROS production, and mitochondrial Ca2+ overload compared to the MDO group.
  • ATP production was increased in the EMPA-treated group.
  • EMPA-secretome treatment preserved cardiomyocyte mitochondrial biogenesis and ameliorated MDO-induced mitochondrial dysfunction.

Conclusions:

  • Empagliflozin treatment, via its effect on the epicardial fat secretome, protects cardiomyocyte mitochondria against metabolic disorder-induced damage.
  • SGLT2is may exert benefits in heart failure and arrhythmias by mitigating mitochondrial oxidative stress and calcium dysregulation.
  • These findings provide mechanistic insights into the cardiovascular advantages of SGLT2 inhibitors.
Keywords:
SGLT2 inhibitorcalcium overloadempagliflozinepicardial fatmitochondriaoxidative stress

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