European journal of pharmacology · 2026
Obesity-associated metabolic dysregulation aggravates myocardial ischemia-reperfusion injury through Gls2-mediated ferroptosis.
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Zhou Taotao, Liu Yang, Xiao Rong, Xie Baodong, Xie Wandong, Qin Xionghai, Zhan Xu, Sun Haobo, Liu Donghui, Qin Sida, Li Changfu, Sun Lihua, Kang Kai
Аннотация
Metabolic diseases, including obesity, are becoming increasingly prevalent worldwide. However, the extent to which obesity-associated metabolic dysregulation exacerbates myocardial ischemia-reperfusion (IR) injury, and its specific impact on the patterns of cell death in this context, remain insufficiently understood. In this study, we demonstrate that obesity-associated metabolic dysregulation leads to more severe cardiac IR injury. This effect is not due to increased IR-mediated myocardial apoptosis, but rather to enhanced IR-induced ferroptosis. Our findings indicate that obesity-associated metabolic dysregulation aggravates cardiac ferroptosis primarily by upregulating glutaminase 2 (Gls2) expression in the heart. Furthermore, inhibition of Gls2 may attenuate IR injury exacerbated by obesity-associated metabolic dysregulation.