Long-term sleep deprivation down-regulates AMPK/SIRT1/PGC-1α pathway and causes lipid metabolism disorder in mice
LIU Xuan1, HU Shuang1, LI Peng-xiang1, ZHANG Rong1, LANG Jing2, WEI Shou-gang1,3
1. Department of Maternal, Child and Adolescent Health, School of Public Health, Capital Medical University, Beijing 100069, China; 2. Weifang Engineering Vocational College, Qingzhou, Shandong 262500, China; 3. Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China
Abstract：Objective To explore the effects of long-term sleep deprivation on adenosine 5'-monophosphate activated protein kinase (AMPK)/ silent information regulation 1 (SIRT1)/ peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α) system in mice. Methods Sixteen 2-month-old C57BL/6J mice were randomly divided into the sleep deprivation group and the normal control group. Sleep deprivation intervention was performed in the sleep deprivation group with a sleep deprivation instrument for 20 hours a day and 6 days a week for 10 consecutive weeks. The control group slept freely for 10 weeks under the same experimental conditions. The body weight was measured once a week. After 10 weeks, the body composition of the mice was measured, and blood, liver and adipose tissue samples were collected to detect the level of serum melatonin, the protein expression levels of main signal molecules in AMPKα, SIRT1, PGC-1α and sterol regulatory element-binding protein 1C (SREBP-1C) in liver tissue, and the expression levels of key enzymes of fat synthesis in adipose tissue, including fatty acid synthase (FAS) and acetyl CoA carbosylase 1(ACC1). Results After modeling, the body weight of mice in the sleep deprivation group was significantly higher than that in the control group (F=10.955, P=0.006), and this difference appeared from the 6th weekend (F=8.535, P=0.012). At the same time, the body fat of mice in the sleep deprivation group was higher than that in the control group ((14.58±1.70)% vs. (11.24±1.64)%, t=4.007, P=0.001). The serum melatonin concentration was lower in the sleep deprivation group than in the control group ((2.33±0.53)ng/ml vs. (2.87±0.23)ng/ml, t=2.643, P=0.019). The expression levels of AMPKa (t= 7.134, P<0.001), SIRT1 (t=7.531, P<0.001) and PGC-1α (t=11.537, P<0.001) in AMPK pathway in the sleep deprivation group decreased, AMPK/SIRT1/PGC-1α pathway was down-regulated, but the expression level of SREBP-1C increased, and the difference was statistically significant (t=-4.496, P=0.001). At the same time, the expression levels of FAS (t=-4.375, P=0.001) and ACC1 in adipose tissue of sleep-deprived mice increased (t=-4.072, P=0.001). Conclusion Long-term sleep deprivation can inhibit the melatonin-mediated AMPK/SIRT1/PGC-1α pathway, and enhance the expression of genes related to fat synthesis, resulting in energy metabolism, especially dysregulation of lipid metabolism homeostasis and increase of body fat.
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2022, Vol. 29 
