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Marine n-3 polyunsaturated fatty acids slow sleep impairment progression by regulating central circadian rhythms in type 2 diabetes

  • 1Department of Endocrinology of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China.
  • 2Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, Zhejiang, China.
  • 3Department of Endocrinology of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China; Department of Nutrition, School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China.
  • 4Cambridge-Su Genomic Resource Center, Suzhou Medical College of Soochow University, Suzhou 215123, Jiangsu, China.
  • 5Department of Endocrinology of The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China; Department of Nutrition, School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China. Electronic address: jingjingjiao@zju.edu.cn.
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May 10, 2025

Abstract

The role of marine n-3 polyunsaturated fatty acids (PUFAs) in promoting sleep has been proposed, yet their benefits for patients with type 2 diabetes (T2D) and the underlying molecular mechanisms remain poorly understood. In this study, we identify a significant association between habitual fish oil use and improved sleep quality in a cohort of 27,549 patients with T2D. A subsequent randomized controlled trial demonstrates that fish oil supplementation enhances sleep parameters in patients with T2D, accompanied by the upregulation of core circadian clock genes, including Clock, Bmal1, and Per2. In vitro, DHA and EPA restore the rhythmic oscillations of key clock genes in hypothalamic neurons disrupted by palmitic acid. Notably, n-3 PUFAs target RORα to regulate circadian clock oscillations and facilitate BMAL1 nuclear translocation. Collectively, our findings highlight the potential of marine n-3 PUFAs as a dietary intervention to improve sleep health in patients with T2D. This study was registered at ClinicalTrials.gov (NCT03708887).

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