Obesity Induces Disruption of Microvascular Endothelial Circadian Rhythm.
Obesity Induces Disruption of Microvascular Endothelial Circadian Rhythm.
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DOI：
10.3389/fphys.2022.887559
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发表时间：
2022
影响因子：
4
通讯作者：
中科院分区：
文献类型：
--
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肥胖者患心血管疾病（CVD）的风险显著升高。此外，肥胖与昼夜节律紊乱有关，表现为异常的睡眠和进食模式。迄今为止，肥胖、昼夜节律紊乱和心血管疾病之间的联系机制尚不完全清楚，迫切需要深入了解新的机制途径，以提高治疗潜力，降低发病率和死亡率。本研究的目的是研究代谢和昼夜节律紊乱在肥胖中的作用，并评估它们在促进血管疾病中的作用。将瘦（db/+）和肥胖（db/db）小鼠置于12周的恒定黑暗中，以区分昼夜节律和昼夜节律，并评估代谢、基因表达和血管功能的变化。内皮型一氧化氮合酶（eNOS），血管健康的必需酶的表达，在肥胖症中是钝化的，并与新的调节剂塞尚（OTUD 7 B）的振荡损失相关。持续黑暗的瘦小鼠显示血管舒张能力明显降低，而肥胖小鼠的内皮功能障碍并没有进一步加剧昼夜侮辱。在肥胖症中，重要的生物钟成分的内皮基因表达发生了改变，但在持续黑暗中饲养的瘦小鼠中不完全表型化，表明肥胖症和昼夜节律紊乱中驱动内皮功能障碍的重叠但独立的机制。总之，这些数据提供了对肥胖症内皮昼夜节律性质的深入了解，并提出了肥胖症导致血管系统独特昼夜节律缺陷的独特机制。
Obese individuals are at significantly elevated risk of developing cardiovascular disease (CVD). Additionally, obesity has been associated with disrupted circadian rhythm, manifesting in abnormal sleeping and feeding patterns. To date, the mechanisms linking obesity, circadian disruption, and CVD are incompletely understood, and insight into novel mechanistic pathways is desperately needed to improve therapeutic potential and decrease morbidity and mortality. The objective of this study was to investigate the roles of metabolic and circadian disruptions in obesity and assess their contributions in promoting vascular disease. Lean (db/+) and obese (db/db) mice were subjected to 12 weeks of constant darkness to differentiate diurnal and circadian rhythms, and were assessed for changes in metabolism, gene expression, and vascular function. Expression of endothelial nitric oxide synthase (eNOS), an essential enzyme for vascular health, was blunted in obesity and correlated with the oscillatory loss of the novel regulator cezanne (OTUD7B). Lean mice subjected to constant darkness displayed marked reduction in vasodilatory capacity, while endothelial dysfunction of obese mice was not further compounded by diurnal insult. Endothelial gene expression of essential circadian clock components was altered in obesity, but imperfectly phenocopied in lean mice housed in constant darkness, suggesting overlapping but separate mechanisms driving endothelial dysfunction in obesity and circadian disruption. Taken together, these data provide insight into the nature of endothelial circadian rhythm in obesity and suggest a distinct mechanism by which obesity causes a unique circadian defect in the vasculature.
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影响因子：
12.3
作者：
Kanbay, Mehmet;Turgut, Faruk;Covic, Adrian
通讯作者：
Covic, Adrian
人类中葡萄糖，脂质和能量代谢的昼夜节律调节。
DOI：
10.1016/j.metabol.2017.11.017
发表时间：
2018-07
期刊：
Metabolism: clinical and experimental
影响因子：
--
作者：
Poggiogalle E;Jamshed H;Peterson CM
通讯作者：
Peterson CM
DOI：
10.3390/medicina56120700
发表时间：
2020-12-15
期刊：
Medicina (Kaunas, Lithuania)
影响因子：
--
作者：
Moczulska B;Zechowicz M;Leśniewska S;Osowiecka K;Gromadziński L
通讯作者：
Gromadziński L
影响因子：
1.1
作者：
Hou, Wang;Jiang, Zhou;Wang, Zhengrong
通讯作者：
Wang, Zhengrong
影响因子：
37.8
作者：
Anea CB;Zhang M;Stepp DW;Simkins GB;Reed G;Fulton DJ;Rudic RD
通讯作者：
Rudic RD