目的:本研究旨在研究睡眠剥夺(SD)在明暗阶段对肝脏和白色脂肪组织(WAT)脂质代谢或脂质代谢调节的影响,并探讨SD对与时钟基因相关的脂质代谢的昼夜影响的可能机制。
方法:2月龄的雄性C57BL/6J小鼠每天剥夺睡眠20小时,连续10天进行弱强迫运动。记录SD和对照小鼠的体重和食物消耗水平,然后在ZT(zeitgeber时间)2和ZT14处死小鼠。外围时钟基因,参与WAT中脂肪合成和分解代谢的酶,和褪黑素信号通路介导的肝脏脂质代谢进行了评估。非靶向代谢组学和串联质量标签(TMT)蛋白质组学用于鉴定肝脏中的差异脂质代谢途径。
结果:体重增加和每日食物消耗在SD后显著升高。观察到WAT中肝脏外周时钟的昼夜调节和参与脂肪合成和分解代谢的酶的明显破坏,强调肝脏脂质代谢途径,而褪黑素信号通路介导的脂质代谢表现出中等变化。
结论:在小鼠中,连续十天的SD增加了体重增加和每日食物消耗。此外,在光明和黑暗时期,SD严重破坏了WAT和肝脏中的脂质代谢。这些昼夜变化可能与周围生物钟的紊乱有关。
OBJECTIVE: This study aimed to examine the effect of sleep deprivation (SD) on lipid metabolism or lipid metabolism regulation in the liver and white adipose tissue (WAT) during the light and dark phases and explored the possible mechanisms underlying the diurnal effect of SD on lipid metabolism associated with clock genes.
METHODS: Male C57BL/6J mice aged 2 months were deprived of sleep daily for 20 h for ten consecutive days with weakly forced locomotion. The body weights and food consumption levels of the SD and control mice were recorded, and the mice were then sacrificed at ZT (zeitgeber time) 2 and ZT 14. The peripheral clock genes, enzymes involved in fat synthesis and catabolism in the WAT, and melatonin signalling pathway-mediated lipid metabolism in the liver were assessed. Untargeted metabolomics and tandem mass tag (TMT) proteomics were used to identify differential lipid metabolism pathways in the liver.
RESULTS: Bodyweight gain and daily food consumption were dramatically elevated after SD. Profound disruptions in the diurnal regulation of the hepatic peripheral clock and enzymes involved in fat synthesis and catabolism in the WAT were observed, with a strong emphasis on hepatic lipid metabolic pathways, while melatonin signalling pathway-mediated lipid metabolism exhibited moderate changes.
CONCLUSIONS: In mice, ten consecutive days of SD increased body weight gain and daily food consumption. In addition, SD profoundly disrupted lipid metabolism in the WAT and liver during the light and dark periods. These diurnal changes may be related to disorders of the peripheral biological clock.