2. Academic Validation
  3. Seipin-Mediated Lipid Droplet Formation in Cardiomyocytes Ameliorates Cardiac Ischemia/Reperfusion Injury

Seipin-Mediated Lipid Droplet Formation in Cardiomyocytes Ameliorates Cardiac Ischemia/Reperfusion Injury

  • Adv Sci (Weinh). 2025 Nov 19:e10203. doi: 10.1002/advs.202510203.
Changyun Liu 1 2,  Junxia Zhang 1 2 3,  Yusi Chen 1,  Geng Shen 4,  Yufei Han 1,  Zihao Zhou 1,  Jinxuan Chen 1,  Xuya Kang 1 2,  Huilin Qu 1 2,  Jiaxin Duanmu 1 2,  Haibao Shang 5,  Yingjia Li 1 2,  Wei Huang 1,  Yan Zhang 1 2 6 7
Affiliations

Affiliations

  • 1 Institute of Cardiovascular Sciences, State Key Laboratory of Vascular Homeostasis and Remodeling, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, 100191, China.
  • 2 Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, Beijing, 100191, China.
  • 3 Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases, Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences, Beijing, 100191, China.
  • 4 Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, China.
  • 5 State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, College of Future Technology, Peking University, Beijing, 100871, China.
  • 6 NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Beijing Key Laboratory of Cardiovascular Receptors Research, Peking University, Beijing, 100191, China.
  • 7 Institute of Cardiovascular Diseases, The First Affiliated Hospital of Dalian Medical University, Dalian, 116021, China.
PMID: 41255216 DOI: 10.1002/advs.202510203
Abstract

Cardiac ischemia/reperfusion (I/R) injury is an important therapeutic target for ischemic heart disease. Lipid droplets (LDs) are the key organelles involved in lipid metabolism. This study aimed to identify the LD-mediated protection against lipotoxicity in cardiac I/R injury. LD accumulation is upregulated in hearts subjected to I/R injury; however, it is insufficient to neutralize lipotoxicity or prevent cardiomyocyte death. Seipin played a central role in LD biogenesis in cardiomyocytes following I/R injury. Seipin deficiency led to reduced LD levels and exacerbated cardiac I/R injury. Whereas increased LD levels, via Seipin overexpression or lipolysis inhibition, ameliorated myocardial I/R injury. I/R-induced downregulation of Seipin is attributed to the reduced expression of its transcription factor USF1, which is required for metabolic adaptation in acute myocardial ischemia. These findings not only elucidate the pathophysiological roles of LDs and Seipin but also provide a promising therapeutic target for myocardial I/R injury.

Keywords

cardiomyocyte death; heart; ischemia/reperfusion injury; lipid droplet; seipin.

Figures
Products