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利用液相色谱-质谱联用技术对OP9-DL1细胞脂肪生成转化进行非靶向代谢组学分析:对胸腺脂肪生成的影响

Untargeted metabolomics analysis of adipogenic transformation in OP9-DL1 cells using liquid chromatography-mass spectrometry: Implications for thymic adipogenesis.

作者信息

Tan Jianxin, Wang Yajun, Wang Siliang, Zhang Nannan, Wu Simeng, Yuan Zhe, Zhu Xike

机构信息

Research Center, Shengjing Hospital of China Medical University, Shenyang, 110004, People's Republic of China.

Department of Medical Oncology, Shengjing Hospital of China Medical University, Shenyang, 110022, People's Republic of China.

出版信息

Cell Biol Int. 2017 Apr;41(4):447-456. doi: 10.1002/cbin.10740. Epub 2017 Feb 21.

DOI:10.1002/cbin.10740
PMID:28185342
Abstract

Adipocyte deposition is a key feature of age-related thymic involution, but the underlying mechanisms responsible for thymic adiposity remain to be elucidated. In the present study, we utilized rosiglitazone, a potent peroxisome proliferator-activated receptor γ agonist, to induce adipogenic differentiation of OP9-DL1 cells, and detected the metabolomics alterations during adipogenic differentiation by using liquid chromatography-mass spectrometry. The obtained metabolites were further processed by multivariate statistical analysis, including principal component analysis, partial least squares discriminant analysis, and orthogonal projection on latent-structures discriminant analysis. As a result, we identified a total of 33 significantly differential metabolites between dimethyl sulphoxide- and rosiglitazone-treated OP9-DL1 cells, which were closely related to the dysregulation of phospholipid metabolism pathway, oxidative stress, and associated amino acid metabolism. Meanwhile, two pathways including glycerophospholipid metabolism and nitrogen metabolism were significantly perturbed (P < 0.05). Collectively, our results may provide some heuristic guidance for addressing the underlying mechanism of thymic adipogenesis, and future studies are warranted to unravel the functions of these altered metabolites in thymic adipogenesis.

摘要

脂肪细胞沉积是与年龄相关的胸腺退化的一个关键特征,但胸腺脂肪化的潜在机制仍有待阐明。在本研究中,我们使用罗格列酮(一种有效的过氧化物酶体增殖物激活受体γ激动剂)诱导OP9-DL1细胞的脂肪生成分化,并通过液相色谱-质谱联用技术检测脂肪生成分化过程中的代谢组学变化。对获得的代谢产物进一步进行多元统计分析,包括主成分分析、偏最小二乘判别分析和潜在结构判别分析的正交投影。结果,我们共鉴定出在二甲基亚砜和罗格列酮处理的OP9-DL1细胞之间有33种显著差异的代谢产物,这些代谢产物与磷脂代谢途径、氧化应激及相关氨基酸代谢的失调密切相关。同时,甘油磷脂代谢和氮代谢这两条途径受到显著干扰(P < 0.05)。总体而言,我们的结果可能为解决胸腺脂肪生成的潜在机制提供一些启发性指导,未来的研究有必要阐明这些改变的代谢产物在胸腺脂肪生成中的作用。

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Label-free quantitative proteomics identifies transforming growth factor β1 (TGF-β1) as an inhibitor of adipogenic transformation in OP9-DL1 cells and primary thymic stromal cells.
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