Abstract

Chronic inflammation that affects primarily metabolic organs, such as white adipose tissue (WAT), is considered as a major cause of human obesity-associated co-morbidities. However, the molecular mechanisms initiating this inflammation in WAT are poorly understood. By combining transcriptomics, ChIP-seq and modeling approaches, we studied the global early and late responses to a high-fat diet (HFD) in visceral (vWAT) and subcutaneous (scWAT) AT, the first being more prone to obesity-induced inflammation. HFD rapidly triggers proliferation of adipocyte precursors within vWAT. However, concomitant antiadipogenic signals limit vWAT hyperplastic expansion by interfering with the differentiation of proliferating adipocyte precursors. Conversely, in scWAT, residing beige adipocytes lose their oxidizing properties and allow storage of excessive fatty acids. This phase is followed by tissue hyperplastic growth and increased angiogenic signals, which further enable scWAT expansion without generating inflammation. Our data indicate that scWAT and vWAT differential ability to modulate adipocyte number and differentiation in response to obesogenic stimuli has a crucial impact on the different susceptibility to obesity-related inflammation of these adipose tissue depots.

中文翻译：

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白色脂肪组织中与肥胖相关的炎症发作时的抗脂肪形成信号

摘要

主要影响新陈代谢器官（例如白色脂肪组织（WAT））的慢性炎症被认为是与人类肥胖相关的合并症的主要原因。但是，人们对WAT中引发这种炎症的分子机制了解甚少。通过结合转录组学，ChIP-seq和建模方法，我们研究了内脏（vWAT）和皮下（scWAT）AT对高脂饮食（HFD）的全球早期和晚期反应，第一个更容易导致肥胖引起的炎症。HFD在vWAT内迅速触发脂肪细胞前体的增殖。然而，伴随的抗脂肪形成信号通过干扰增殖性脂肪细胞前体的分化来限制vWAT增生性扩张。相反，在scWAT中，残留的米色脂肪细胞失去其氧化特性，并允许储存过多的脂肪酸。此阶段之后是组织增生性生长和血管生成信号的增加，这进一步使scWAT扩展而不会产生炎症。我们的数据表明，scWAT和vWAT调节脂肪细胞数量和分化的能力，以响应致肥胖性刺激，对这些脂肪组织储库的肥胖相关炎症的敏感性不同，具有至关重要的影响。