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通过转录谱的系统综合预测脂肪棕色化能力。

Prediction of Adipose Browning Capacity by Systematic Integration of Transcriptional Profiles.

机构信息

Gene Center, Department of Biochemistry, Ludwig-Maximilians Universität München, 81377 Munich, Germany; Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München and German National Diabetes Center (DZD), 85764 Neuherberg, Germany.

Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München and German National Diabetes Center (DZD), 85764 Neuherberg, Germany.

出版信息

Cell Rep. 2018 Jun 5;23(10):3112-3125. doi: 10.1016/j.celrep.2018.05.021.

Abstract

Activation and recruitment of thermogenic cells in human white adipose tissues ("browning") can counteract obesity and associated metabolic disorders. However, quantifying the effects of therapeutic interventions on browning remains enigmatic. Here, we devise a computational tool, named ProFAT (profiling of fat tissue types), for quantifying the thermogenic potential of heterogeneous fat biopsies based on prediction of white and brown adipocyte content from raw gene expression datasets. ProFAT systematically integrates 103 mouse-fat-derived transcriptomes to identify unbiased and robust gene signatures of brown and white adipocytes. We validate ProFAT on 80 mouse and 97 human transcriptional profiles from 14 independent studies and correctly predict browning capacity upon various physiological and pharmacological stimuli. Our study represents the most exhaustive comparative analysis of public data on adipose biology toward quantification of browning after personalized medical intervention. ProFAT is freely available and should become increasingly powerful with the growing wealth of transcriptomics data.

摘要

生热细胞在人体白色脂肪组织中的激活和募集(“褐变”)可以对抗肥胖及其相关的代谢紊乱。然而,量化治疗干预对褐变的影响仍然是一个谜。在这里,我们设计了一种名为 ProFAT(脂肪组织类型分析)的计算工具,用于根据原始基因表达数据集预测白色和棕色脂肪细胞的含量来量化异质脂肪活检的生热潜力。ProFAT 系统地整合了 103 个来自小鼠脂肪组织的转录组,以鉴定棕色和白色脂肪细胞的无偏和稳健的基因特征。我们在 14 项独立研究的 80 只小鼠和 97 个人类转录谱上验证了 ProFAT,并在各种生理和药理学刺激下正确预测了褐变能力。我们的研究代表了对脂肪生物学的公共数据进行的最详尽的比较分析,以量化个性化医疗干预后的褐变。ProFAT 是免费提供的,并且随着转录组数据的不断丰富,它的功能将会越来越强大。

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