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May 6, 2023Diabetology & Metabolic SyndromeOpen Access

Empagliflozin improves LVEF by ~15% in diabetic mice by promoting BCAA catabolism to enhance autophagy.

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Why the study?

Empagliflozin reduces heart failure risk, but the underlying mechanisms remain elusive; this study investigated its effect on branched-chain amino acid metabolism in diabetic cardiomyopathy.

Does empagliflozin improve cardiac structure and function in a mouse model of diabetic cardiomyopathy?

Population

Thirty male 8-week KK Cg-Ay/J diabetic mice and fifteen male 8-week C57BL/6J control mice

Comparison

Empagliflozin (3.75 mg/kg/day) vs diabetic model vs non-diabetic control

Design

Preclinical animal study

Follow-up

16 weeks

Key result

Empagliflozin significantly improved left ventricular ejection fraction and attenuated myocardial injury in diabetic mice by promoting branched-chain amino acid catabolism and inhibiting mTOR/p-ULK1 to enhance autophagy.

Authors

LZLin ZhangHZHeming ZhangXXXiuzhu Xie

Discussion

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Member takes

Overview

Should not change clinical practice; hypothesis-generating for empagliflozin in diabetic cardiomyopathy.

Structured PICO

Does empagliflozin improve cardiac structure and function in a mouse model of diabetic cardiomyopathy?

P
Population
45 male 8-week mice (30 KK Cg-Ay/J mice as a diabetic cardiomyopathy model, 15 C57BL/6J mice as controls)
I
Intervention
Empagliflozin 3.75 mg/kg/day by gavage daily for 16 weeks
C
Comparator
Diabetic model group (no empagliflozin) and non-diabetic control group (no intervention)
O
Outcome
Cardiac structure and function (evaluated by echocardiography and histopathology), and molecular mechanisms (proteomics, BCAA metabolism, autophagy)surrogate

Main Result

Absolute Event Rate: 52.2% vs 37.6%

p-value: p=0.005

Empagliflozin attenuates diabetic cardiomyopathy in mice by promoting branched-chain amino acid catabolism and enhancing autophagy via mTOR/p-ULK1 inhibition.

Limitations

  • Animal study, results may not directly translate to humans
  • The mechanism of how empagliflozin up-regulates PP2Cm remains to be revealed in further studies

Cite This Study

Zhang et al. (2023) studied Diabetic cardiomyopathy (n=45). Empagliflozin vs. No treatment was evaluated on Left ventricle ejection fraction (EF) (p=0.005). Empagliflozin significantly improved left ventricular ejection fraction and attenuated myocardial injury in diabetic mice by promoting branched-chain amino acid catabolism and inhibiting mTOR/p-ULK1 to enhance autophagy.

synapsesocial.com/papers/6a10b4f6cfa01e990d9f5cf2https://doi.org/10.1186/s13098-023-01061-6
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