Melatonin, a circadian hormone, has been reported to improve host lipid metabolism by reprogramming the gut microbiota, which also exhibits rhythmicity in a light/dark cycle. However, the effect of the administration of exogenous melatonin on the diurnal variation in the gut microbiota in high-fat diet (HFD)-fed mice is unclear. Here, we further confirmed the antiobesogenic effect of melatonin on mice fed an HFD for two weeks. Samples were collected every 4 h within a 24-h period, and diurnal rhythms of clock gene expression (Clock, Cry1, Cry2, Per1, and Per2) and serum lipid indexes varied with diurnal time. Notably, Clock and triglycerides (TGs) showed a marked rhythm in the control and melatonin-treated mice but not in the HFD-fed mice. The rhythmicity of these parameters was similar between the control and melatonin-treated HFD-fed mice compared with the HFD group, indicating an improvement caused by melatonin in the diurnal clock of host metabolism in HFD-fed mice. Moreover, 16S rDNA sequencing showed that most microbes exhibited daily rhythmicity, and the trends were different for different groups and at different time points. We also identified several specific microbes correlated with the circadian clock genes and serum lipid indexes, which might indicate the potential mechanism of action of melatonin in HFD-fed mice. In addition, effects of melatonin exposure during daytime or nighttime were compared, but nonsignificant difference was noticed in response to HFD-induced lipid dysmetabolism. Interestingly, the responses of microbiota-transplanted mice to HFD feeding also varied at different transplantation times (8:00 and 16:00) and with different microbiota donors. In summary, the daily oscillations in the expression of circadian clock genes, serum lipid indexes, and the gut microbiota appeared to be driven by short-term feeding of an HFD, while administration of exogenous melatonin improved the composition and diurnal rhythmicity of the gut microbiota in HFD-fed mice.
Keywords: melatonin, circadian clock, gut microbiota, lipid dysmetabolism