Rewiring marine n-3 polyunsaturated fatty acids as circadian rhythm regulators for manipulating glycolipid metabolism: emerging insights into molecular mechanism and potential targets

The 24-hour rhythm substantially affects the daily life activities of all living organisms on Earth. In this review, we unravel the role of marine n-3 polyunsaturated fatty acids (PUFAs) as circadian rhythm regulators in glycolipid metabolism disorders. As two major types of n-3 PUFAs, docosahexaenoic acid (DHA) improves circadian rhythms by insulin-induced gene 2–sterol-regulatory element–binding protein pathway, while eicosapentaenoic acid (EPA) targets melatonin to regulate circadian rhythms. Given GABAergic neurons in the hypothalamic suprachiasmatic nucleus clock to the hypothalamic–pituitary–adrenal axis, DHA and EPA directly target G protein–coupled receptor 120 (GPR120) on cellular membrane and then manipulate circadian rhythm genes Rev-erb and RORα to improve glucose metabolism. Furthermore, n-3 PUFAs directly respond on GPR120 and peroxisome proliferator-activated receptor γ (PPARγ), which in turn affect circadian genes Per, Bmal1, and Rev-erbα and then ameliorate lipid metabolism disorders. The current review broadens the functionality of n-3 PUFAs in the field of circadian rhythm regulation and concludes molecular mechanisms on regulating glycolipid metabolism through adjusting circadian rhythms.