Diabetic human adipose tissue-derived mesenchymal stem cells fail to differentiate in functional adipocytes (Publication with Expression of Concern)
Diabetic human adipose tissue-derived mesenchymal stem cells fail to differentiate in functional adipocytes (Publication with Expression of Concern)
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DOI：
10.1177/1535370216681552
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发表时间：
2017-05-01
影响因子：
3.2
通讯作者：
Vanella, Luca
中科院分区：
文献类型：
--
作者：
Barbagallo, Ignazio;Li Volti, Giovanni;Vanella, Luca
脂肪组织功能障碍是糖尿病患者的标志，是该组织稳态改变的结果。间充质干细胞（MSCs）及其向脂肪细胞的分化在维持成人脂肪组织的质量和功能方面有重要作用。本研究的目的是评估来自患有2型糖尿病（dASC）的患者的MSC的分化，以及这种过程如何导致增生，或者更确切地说，停止脂肪细胞更新，导致成熟脂肪细胞肥大。我们的结果表明，所有成脂标志物的基因谱在分化后的糖尿病细胞中均不表达，这表明糖尿病细胞未能分化为脂肪细胞。有趣的是，与从健康受试者获得的细胞相比，在dASC中发现δ样1、过氧化物酶体增殖物激活受体α和白细胞介素1 β上调，而Sirtuin 1和胰岛素受体底物1基因表达下调。总之，我们的数据表明，dASC失去了分化为成熟和功能性脂肪细胞的能力。总之，我们的体外研究是第一个表明，糖尿病患者可能会发展肥胖症，通过现有的成熟脂肪细胞的肥大，由于失败营业额的脂肪tissue.Impact statementIn本手稿，我们评估了间充质干细胞（MSC）的分化潜力，从健康和糖尿病患者的脂肪细胞。这一发现可能是巨大的潜在利益领域的肥胖，以利用这些结果，以进一步了解代谢综合征的病理生理过程。特别是，糖尿病患者的炎症导致MSC分化功能障碍和脂肪细胞周转减少，导致胰岛素抵抗。
Adipose tissue dysfunction represents a hallmark of diabetic patients and is a consequence of the altered homeostasis of this tissue. Mesenchymal stem cells (MSCs) and their differentiation into adipocytes contribute significantly in maintaining the mass and function of adult adipose tissue. The aim of this study was to evaluate the differentiation of MSCs from patients suffering type 2 diabetes (dASC) and how such process results in hyperplasia or rather a stop of adipocyte turnover resulting in hypertrophy of mature adipocytes. Our results showed that gene profile of all adipogenic markers is not expressed in diabetic cells after differentiation indicating that diabetic cells fail to differentiate into adipocytes. Interestingly, delta like 1, peroxisome proliferator-activated receptor alpha, and interleukin 1 beta were upregulated whereas Sirtuin 1 and insulin receptor substrate 1 gene expression were found downregulated in dASC compared to cells obtained from healthy subjects. Taken together our data indicate that dASC lose their ability to differentiate into mature and functional adipocytes. In conclusion, our invitro study is the first to suggest that diabetic patients might develop obesity through a hypertrophy of existing mature adipocytes due to failure turnover of adipose tissue.Impact statementIn the present manuscript, we evaluated the differentiative potential of mesenchymal stem cells (MSCs) in adipocytes obtained from healthy and diabetic patients. This finding could be of great potential interest for the field of obesity in order to exploit such results to further understand the pathophysiological processes underlying metabolic syndrome. In particular, inflammation in diabetic patients causes a dysfunction in MSCs differentiation and a decrease in adipocytes turnover leading to insulin resistance.