目前已经证实睡眠不足增加心血管病风险，研究链接睡眠不足与心血管损伤的分子机制是心血管病防治的重要窗口。前期本课题组利用大型前瞻性队列和GWAS研究结果，发现脂联素、瘦素很可能是链接儿童青少年睡眠不足与心血管病风险的关键因子。我们首次发现脂联素受体基因CDH13为控制左心室重塑的极具潜力的遗传靶点。同时，睡眠时间与该基因的交互作用，睡眠时间减少可以显著削弱该基因位点对心脏结构的保护效应。因此，我们提出脂联素、瘦素介导的“脑-心轴”代谢调节通路，并以睡眠不足导致的心脏损伤为切入点，研究动物生命不同时期睡眠不足与对照组心脏重构和修复能力的差异，并观察这些差异与脂联素、瘦素调节的关系。此外，本研究从细胞水平验证在临床研究上的发现，从多水平多层次证实脂联素、瘦素介导的“脑-心轴”代谢调节通路在睡眠不足导致心脏损伤的机制，为心血管疾病防治提供了新的方向。

Sleep insufficiency has been shown to increase cardiovascular disease risk , and the study of the molecular mechanism linking sleep insufficiency and cardiovascular injury is a key event for the prevention and treatment of cardiovascular disease.Our previous large prospective cohort and GWAS studies have found that adiponectin and leptin are likely to be the key factors linking sleep insufficiency and cardiovascular risk in children and adolescents.This is the first study to identify the adiponectin receptor gene CDH13 as a key locus for cardiac remodeling.CDH13 rs4783244 was significantly correlated with adiponectin levels (p=8.07×10−7).The adiponectin-rising allele in rs4783244 locus was significantly associated with decreased LVMI( LVMI serves as an important marker for myocardial remodeling) (p = 6.99×10−4) after adjusting for classical cardiovascular risk factors, and further for adiponectin levels,while no significant association was found between the other loci and LVMI. At the same time, the genetic association was more evident in longer sleep duration while lost in short sleep duration,and CDH13 rs4783244 confers stronger cardio-protection in longer sleep duration when contrasted with short sleep duration.Therefore, we proposed the "brain-cardiac axis" metabolic regulation pathway mediated by adiponectin and leptin.In addition,taking the heart injury caused by sleep insufficiency as the entry point, we studied the differences in the cardiac remodeling and repair ability between the sleep insufficiency group and the control group in different periods of animal life, and observed the relationship between these differences and the regulation of adiponectin and leptin .Besides, this study verified the findings in clinical studies at the cellular level, and confirmed the mechanism of the "brain-cardiac axis" metabolic regulation pathway mediated by adiponectin and leptin in the heart injury caused by sleep insufficiency at multiple levels, providing a new direction for the prevention and treatment of cardiovascular disease.