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

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).