AUTHOR=Song Min-Woo , Cui Wenhao , Lee Chang-Gun , Cui Rihua , Son Young Ho , Kim Young Ha , Kim Yujin , Kim Hae Jin , Choi Sung-E. , Kang Yup , Kim Tae Ho , Jeon Ja Young , Lee Kwan-Woo TITLE=Protective effect of empagliflozin against palmitate-induced lipotoxicity through AMPK in H9c2 cells JOURNAL=Frontiers in Pharmacology VOLUME=14 YEAR=2023 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2023.1228646 DOI=10.3389/fphar.2023.1228646 ISSN=1663-9812 ABSTRACT=

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently emerged as novel cardioprotective agents. However, their direct impact on cardiomyocyte injury is yet to be studied. In this work, we investigate the underlying molecular mechanisms of empagliflozin (EMPA), an SGLT2 inhibitor, in mitigating palmitate (PA)-induced cardiomyocyte injury in H9c2 cells. We found that EMPA significantly attenuated PA-induced impairments in insulin sensitivity, ER stress, inflammatory cytokine gene expression, and cellular apoptosis. Additionally, EMPA elevated AMP levels, activated the AMPK pathway, and increased carnitine palmitoyl transferase1 (CPT1) gene expression, which collectively enhanced fatty acid oxidation and reduced stress signals. This study reveals a novel mechanism of EMPA’s protective effects against PA-induced cardiomyocyte injury, providing new therapeutic insights into EMPA as a cardioprotective agent.