Li Haoyu, Zhuang Pan, Liu Xiaohui, Li Yin, Ao Yang, Tian Yimei, Jia Wei, Zhang Yu, Jiao Jingjing
Department of Endocrinology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China.
National Engineering Laboratory of Intelligent Food Technology and Equipment, Zhejiang Key Laboratory of Agri-food Reources and High-value Utilization, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang, China.
Research (Wash D C). 2025 Apr 29;8:0683. doi: 10.34133/research.0683. eCollection 2025.
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have been proposed to benefit cardiometabolic health. However, the relationship between the intake of DHA and EPA and type 2 diabetes (T2D) risk remains equivocal, and the effects of DHA and EPA on skeletal muscle, the primary organ for glucose metabolism, merit further investigation. Here, we show that habitual fish oil supplementation was associated with a 9% lower T2D risk and significantly interacted with variants at GLUT4 in a prospective cohort of 48,358 people with prediabetes. Muscular metabolome analysis in the animal study revealed that DHA and EPA altered branched-chain amino acids, creatine, and glucose oxidation-related metabolites, concurrently with elevated muscular glycogen synthase and pyruvate dehydrogenase contents that promoted glucose disposal. Further myotube investigation revealed that DHA and EPA promoted muscular GLUT4 translocation by elevating Rab GTPases and target-SNARE expression. Together, DHA and EPA supplementation provides a promising approach for T2D prevention through targeting muscular glucose homeostasis, including enhancing GLUT4 translocation, glycogen synthesis, and aerobic glycolysis.
二十二碳六烯酸（DHA）和二十碳五烯酸（EPA）被认为对心脏代谢健康有益。然而，DHA和EPA的摄入量与2型糖尿病（T2D）风险之间的关系仍不明确，DHA和EPA对骨骼肌（葡萄糖代谢的主要器官）的影响值得进一步研究。在此，我们表明，在一项针对48358名糖尿病前期患者的前瞻性队列研究中，长期补充鱼油与T2D风险降低9%相关，并且与GLUT4基因变异存在显著相互作用。动物研究中的肌肉代谢组分析显示，DHA和EPA改变了支链氨基酸、肌酸以及与葡萄糖氧化相关的代谢物，同时肌肉糖原合酶和丙酮酸脱氢酶含量升高，促进了葡萄糖的代谢。进一步的肌管研究表明，DHA和EPA通过提高Rab GTP酶和靶标-SNARE的表达促进肌肉GLUT4转位。总之，补充DHA和EPA通过针对肌肉葡萄糖稳态，包括增强GLUT4转位、糖原合成和有氧糖酵解，为预防T2D提供了一种有前景的方法。
