Selective sodium-glucose cotransporter two inhibitor empagliflozin ameliorates diabetic cardiomyopathy by activating the AMPK/TFEB signaling pathway.
Journal
Journal of food and drug analysis
Journal Volume
33
Journal Issue
4
Start Page
6
ISSN
2224-6614
Date Issued
2025-12-15
Author(s)
Hsu, Man-Chen
Chang, Ru-Wen
Wang, Mu-Chun
Chen, Chia-Hui
Chen, Wen-Hua
Wang, Chih-Hsien
Abstract
The highly selective SGLT2 inhibitor (SGLT2i) is reported to have beneficial effects on diabetic cardiac hypertrophy; however, the molecular mechanisms underlying the cardioprotection of SGLT2i are not fully understood. In this study, we investigated the impact of the SGLT2 Inhibitor empagliflozin (EMPA) on diabetic hearts and its regulatory mechanisms in high-fat-diet (HFD)- and streptozotocin (STZ)-treated rats. Male rats orally administered HFD/STZ treatment for eight weeks, with or without EMPA (10 mg/kg), were used as our in vivo model. Hematoxylin and eosin (H&E) staining was used for histological examination. Western blot analysis and immunohistochemistry were used to analyze the expression of proteins. Daily EMPA administration prevented the HFD/STZ treatment-induced cardiac hypertrophy by activating the AMP-activated protein kinase (AMPK)/transcription factor EB (TFEB)-mediated upregulation of autophagy- and antioxidant-related proteins. Moreover, EMPA treatment decreased oxidative stress by increasing the antioxidant capacity and protein expression of antioxidant proteins while downregulating the levels of 4-hydroxy-2E-nonenal in the hearts of diabetic rats. Furthermore, EMPA treatment decreased cardiomyocyte apoptosis and increased heart mitochondrial function. The AMPK/TFEB signaling-mediated increase in autophagy, antioxidant capacity, mitochondrial function, and attenuated cardiomyocyte apoptosis may be crucial in the anti-hypertrophic effect conferred by SGLT2i. Our clinical implications suggest a novel pharmacological approach for treating diabetic cardiomyopathy by modulating autophagy and redox homeostasis.
Type
journal article