Chronic circadian shift leads to adipose tissue inflammation and fibrosis.
Chronic circadian shift leads to adipose tissue inflammation and fibrosis.
复制标题
慢性昼夜节律改变会导致脂肪组织炎症和纤维化。
DOI：
10.1016/j.mce.2020.111110
复制
发表时间：
2021-02-05
影响因子：
4.1
通讯作者：
Ma K
中科院分区：
文献类型：
--
作者：
Xiong X;Lin Y;Lee J;Paul A;Yechoor V;Figueiro M;Ma K
昼夜节律钟发挥代谢途径的时间协调作用。生物钟中断与肥胖和胰岛素抵抗的发展密切相关，我们以前的研究发现，重要的生物钟转录激活因子脑和肌肉Arnt样1（Bmal 1）是脂肪形成的关键调节因子。然而，慢性轮班工作对脂肪组织的代谢后果尚未明确界定。在这里，使用环境照明诱导的时钟中断，模仿旋转轮班时间表，我们表明，慢性时钟失调6个月的小鼠导致惊人的脂肪细胞肥大与脂肪组织炎症和纤维化。内脏和皮下贮库均显示增大的脂肪细胞，具有突出的冠状结构，表明巨噬细胞浸润以及细胞外基质重塑的证据。这些脂肪库的全球转录组学分析显示，轮班工作导致炎症，脂肪形成和血管生成途径的上调，破坏了正常的时间依赖性调节。脂肪组织中的这些变化与轮班小鼠中受损的胰岛素信号传导以及mTOR信号传导途径的抑制相关。综上所述，我们的研究确定了慢性轮班工作方案引起的显著的脂肪储存功能障碍，这可能是昼夜节律失调和胰岛素抵抗之间联系的基础。
The circadian clock exerts temporal coordination of metabolic pathways. Clock disruption is intimately linked with the development of obesity and insulin resistance, and our previous studies found that the essential clock transcription activator, Brain and Muscle Arnt-like 1 (Bmal1), is a key regulator of adipogenesis. However, the metabolic consequences of chronic shiftwork on adipose tissues have not been clearly defined. Here, using an environmental lighting-induced clock disruption that mimics rotating shiftwork schedule, we show that chronic clock dysregulation for 6 months in mice resulted in striking adipocyte hypertrophy with adipose tissue inflammation and fibrosis. Both visceral and subcutaneous depots display enlarged adipocyte with prominent crown-like structures indicative of macrophage infiltration together with evidence of extracellular matrix remodeling. Global transcriptomic analyses of these fat depots revealed that shiftwork resulted in up-regulations of inflammatory, adipogenic and angiogenic pathways with disruption of normal time-of-the-day-dependent regulation. These changes in adipose tissues are associated with impaired insulin signaling in mice subjected to shiftwork, together with suppression of the mTOR signaling pathway. Taken together, our study identified the significant adipose depot dysfunctions induced by chronic shiftwork regimen that may underlie the link between circadian misalignment and insulin resistance.
登录
查看更多内容
影响因子：
16.2
作者：
Cao R;Robinson B;Xu H;Gkogkas C;Khoutorsky A;Alain T;Yanagiya A;Nevarko T;Liu AC;Amir S;Sonenberg N
通讯作者：
Sonenberg N
DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
--
作者：
Chatterjee S;Ma K
通讯作者：
Ma K
影响因子：
29
作者：
Chaix A;Lin T;Le HD;Chang MW;Panda S
通讯作者：
Panda S
影响因子：
29
作者：
Hatori M;Vollmers C;Zarrinpar A;DiTacchio L;Bushong EA;Gill S;Leblanc M;Chaix A;Joens M;Fitzpatrick JA;Ellisman MH;Panda S
通讯作者：
Panda S