Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Department of Gynecology and Obstetrics, School of Medicine, J. W. Goethe University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
Stem Cell Reports. 2018 Feb 13;10(2):583-599. doi: 10.1016/j.stemcr.2017.12.022. Epub 2018 Jan 27.
Adipose-derived mesenchymal stem cells (ASCs) have crucial functions, but their roles in obesity are not well defined. We show here that ASCs from obese individuals have defective primary cilia, which are shortened and unable to properly respond to stimuli. Impaired cilia compromise ASC functionalities. Exposure to obesity-related hypoxia and cytokines shortens cilia of lean ASCs. Like obese ASCs, lean ASCs treated with interleukin-6 are deficient in the Hedgehog pathway, and their differentiation capability is associated with increased ciliary disassembly genes like AURKA. Interestingly, inhibition of Aurora A or its downstream target the histone deacetylase 6 rescues the cilium length and function of obese ASCs. This work highlights a mechanism whereby defective cilia render ASCs dysfunctional, resulting in diseased adipose tissue. Impaired cilia in ASCs may be a key event in the pathogenesis of obesity, and its correction might provide an alternative strategy for combating obesity and its associated diseases.
脂肪间充质干细胞（ASCs）具有重要的功能，但它们在肥胖中的作用尚未明确。我们发现肥胖个体来源的 ASC 初级纤毛存在缺陷，表现为纤毛缩短且无法正常响应刺激。纤毛功能障碍会影响 ASC 的功能。暴露于肥胖相关的低氧和细胞因子会缩短瘦 ASC 的纤毛。与肥胖 ASC 类似，经白细胞介素 6 处理的瘦 ASC 中 Hedgehog 通路受损，其分化能力与纤毛解组装基因（如 AURKA）的增加相关。有趣的是，抑制 Aurora A 或其下游靶标组蛋白去乙酰化酶 6 可恢复肥胖 ASC 的纤毛长度和功能。这项工作强调了一种机制，即纤毛缺陷使 ASC 功能失调，导致病态脂肪组织。ASCs 中的纤毛功能障碍可能是肥胖发病机制中的一个关键事件，其纠正可能为对抗肥胖及其相关疾病提供一种替代策略。
