Admistration of Exogenous Melatonin Improves the Diurnal Rhythms of Gut Microbiota in High Fat Diet-Fed Mice

Abstract

22Melatonin, a circadian hormone, has been reported to improve host lipid metabolism 23 by reprogramming gut microbiota, which also exhibits rhythmicity in a light/dark 24 cycle. However, the effect of admistartion of exogenous melatonin on the diurnal 25 78 compositions [16]. We further confirmed the underlying mechanism of melatonin in 79 HFD-induced lipid dysmetabolism which may be associated with reprogramming gut 80 microbiota, especially, Bacteroides and Alistipes-mediated acetic acid production 81 [17]. 82Gut microbiota is highly shaped by dietary HFD and obese human and animals are 83 characterized by lower diversity and impaired gut microbiota compositions, especially 84 for Firmicutes and Bacteroidetes abundances [18][19][20][21]. Interestingly, several reports 85 have revealed that the gut microbiota and its metabolites exhibit circadian rhythm, 86 which are driven by HFD [22][23][24][25]. Also, some microbe has been reported to be 87 sensitive to melatonin [26], but the role of melatonin in the regulation of the diurnal 88 patterns of gut microbial structure and function, and whether gut microbiota 89 oscillations are associated with the anti-obese effect of melatonin is not yet known. 90In this study we further analyzed the short-time effect of HFD feeding on diurnal 91 variations in gut microbiota and the relationship between gut microbiota oscillations 92 and the expression of circadian clock genes and serum lipids. 93 94 2. Materials and methods 95 2.1 Animal and diet 96 ICR mice were purchased from SLAC Laboratory Animal Central (Changsha, China). 97All animals had free access to food and drinking water (temperature, 25±2°C; relative 98 humidity, 45-60%; lighting cycle, 12 h/d) during the experiment. Diets used in this 99 study were according to our previous study [17]. As sex produces difference in 100 melatoin profile [27], only female mice were used in this study to rule out the gender 101 interference. 102 103 2.2 Melatonin treatment 104 126 Female mice (22.77 ± 0.10 g, about 4 week) were randomly grouped to control 105 (Cont), HFD, and HFD plus melatonin (MelHF) groups (n=42). Mice in MelHF group 106 received the HFD and melatonin water (0.4 mg/mL melatonin, Meilun, Dalian, China, 107 directly diluted in drinking water) [17]. The melatonin solution was prepared daily 108 and kept in a normal bottle with an aluminum foil cover to prevent light-induced 109 degradation of melatonin. After two weeks of melatonin administration, 6 mice in