肥胖实质是脂肪过量蓄积。睡眠不足和夜间光暴露皆能增加肥胖发生危险性，尤其对于儿童青少年的影响更甚，但其致病机理尚不明了，以至目前肥胖的群体防治措施仅局限于膳食和运动干预，防治效果不佳，肥胖发生率持续攀升。本项目以动物为实验对象，研究睡眠不足和夜间光暴露对脂肪合成与分解代谢平衡的影响。提出了睡眠不足和夜间光暴露可造成生物钟紊乱、褪黑素介导的脂代谢失调和瘦素抵抗，从而使机体脂肪生成大于分解产热的假说。研究主要采用Western blot等方法，探析睡眠剥夺和夜间光暴露对小鼠下丘脑与脂肪组织钟基因、肝脏褪黑素膜受体与核受体介导的脂代谢通路关键基因及调节因子、脑与脂肪组织瘦素信号通路及调节因子表达的影响，着重两因素的复合暴露效应、长期暴露效应、暴露期补充褪黑素效应、去暴露后的恢复效应等，旨在揭示睡眠不足和夜间光暴露扰乱脂代谢平衡促发肥胖的分子机制，为肥胖防治提供新的措施和分子靶点。

Obesity is the excessive accumulation and storage of fat in the body. Epidemiological studies have demonstrated that sleep insufficiency and night light exposure both can increase the risk of obesity, especially for children and adolescents, but the underlying mechanisms remain unclear. As a result, the current obesity prevention and control measures are still confined to diet and exercise, and the effectiveness were not satisfied, with obesity rates continuing to rise worldwidely, affecting countries rich and poor. This project is aimed to provide insights into the mechanisms for the obesity-promoting effects of sleep insufficiency and night light exposure, by investigating their influences on the balance between lipogenesis and lipolysis, based on animal experiments and combined with human trials. The central hypothesis is that sleep insufficiency and night light exposure may lead to increased adipogenesis and/or decreased lipolysis and fatty acid oxidation, which is prone to the occurrence and development of obesity, due to disruption of peripheral circadian clocks in adipose tissues and dysregulation of melatonin- and leptin-mediated lipid metabolic pathways. Western blot technique was mainly used to analyze the altered expression of clock and metabolic genes after intervention in C57BL/6J mice, including circadian genes BMAL1, PER2, RORα、β、ɤ, REV-ERBα、β, and HDAC3 in adipose tissues, key metabolic genes and other regulatory proteins involved in melatonin membrane receptors-, melatonin nuclear receptors- and leptin receptor-based lipid metabolic pathways, with special attention being paid to the joint effects of the two interference factors, the long-term effects, the effects of melatonin supplementation during intervention, the recovery effects after intervention, and the change of leptin sensitivity. This project is expected to provide primary in-vivo evidences that sleep insufficiency and night light exposure be obesity risk factors, and that new macro-measures, techniques and even molecular biological targets can be taken into consideration in obesity prevention and treatment.