Eicosapentaenoic acid induces macrophage Mox polarization to prevent diabetic cardiomyopathy

  • EMBO Rep. 2024 Dec;25(12):5507-5536. doi: 10.1038/s44319-024-00271-x.
Jie Li  #  1  2 ,  Wenshan Nan  #  1  3 ,  Xiaoli Huang  4 ,  Huali Meng  1  2 ,  Shue Wang  5 ,  Yan Zheng  1 ,  Ying Li  1 ,  Hui Li  6 ,  Zhiyue Zhang  6 ,  Lei Du  1  2 ,  Xiao Yin  7 ,  Hao Wu  8  9  10
Affiliations
  • 1. Research Center of Translational Medicine, Jinan Central Hospital, Shandong University, 105 Jiefang Rd., Jinan, Shandong, 250013, China.
  • 2. Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Rd., Jinan, Shandong, 250012, China.
  • 3. Department of Endocrinology and Metabolism, Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, 105 Jiefang Rd., Jinan, Shandong, 250013, China.
  • 4. Department of Nutrition, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 107 Wenhua Xi Rd., Jinan, Shandong, 250012, China.
  • 5. Experimental Center of Public Health and Preventive Medicine, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Rd., Jinan, Shandong, 250012, China.
  • 6. NMPA Key Laboratory for Technology Research and Evaluation of Drug Products, Key Laboratory of Chemical Biology (Ministry of Education), Department of Pharmaceutics, School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Rd., Jinan, Shandong, 250012, China.
  • 7. Department of Endocrinology and Metabolism, Central Hospital Affiliated to Shandong First Medical University, Shandong First Medical University, 105 Jiefang Rd., Jinan, Shandong, 250013, China. [email protected].
  • 8. Research Center of Translational Medicine, Jinan Central Hospital, Shandong University, 105 Jiefang Rd., Jinan, Shandong, 250013, China. [email protected].
  • 9. Department of Nutrition and Food Hygiene, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhua Xi Rd., Jinan, Shandong, 250012, China. [email protected].
  • 10. Shandong Provincial Engineering and Technology Research Center for Food Safety Monitoring and Evaluation, 44 Wenhua Xi Rd., Jinan, Shandong, 250012, China. [email protected].
  • # Contributed equally.
PMID: 39482491 DOI: 10.1038/s44319-024-00271-x
Abstract

Diabetic cardiomyopathy (DC) leads to heart failure, with few effective approaches for its intervention. Eicosapentaenoic acid (EPA) is an essential nutrient that benefits the cardiovascular system, but its effect on DC remains unknown. Here, we report that EPA protects against DC in streptozotocin and high-fat diet-induced diabetic mice, with an emphasis on the reduction of cardiac M1-polarized macrophages. In vitro, EPA abrogates cardiomyocyte injury induced by M1-polarized macrophages, switching macrophage phenotype from M1 to Mox, but not M2, polarization. Moreover, macrophage Mox polarization combats M1-polarized macrophage-induced cardiomyocyte injury. Further, heme oxygenase 1 (HO-1) was identified to maintain the Mox phenotype, mediating EPA suppression of macrophage M1 polarization and the consequential cardiomyocyte injury. Mechanistic studies reveal that G-protein-coupled receptor 120 mediates the upregulation of HO-1 by EPA. Notably, EPA promotes Mox polarization in monocyte-derived macrophages from diabetic patients. The current study provides EPA and macrophage Mox polarization as novel strategies for DC intervention.

Keywords
Diabetic Cardiomyopathy; Eicosapentaenoic Acid; Heme Oxygenase 1; Macrophage; Mox Polarization.
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