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Multiomics reveal unique signatures of human epiploic adipose tissue related to systemic insulin resistance
Gut ( IF 24.5 ) Pub Date : 2022-11-01 , DOI: 10.1136/gutjnl-2021-324603
Laura Krieg 1 , Konrad Didt 2 , Isabel Karkossa 1 , Stephan H Bernhart 3 , Stephanie Kehr 3 , Narmadha Subramanian 4 , Andreas Lindhorst 5 , Alexander Schaudinn 6 , Shirin Tabei 7 , Maria Keller 8 , Michael Stumvoll 9 , Arne Dietrich 10 , Martin von Bergen 1, 11 , Peter F Stadler 3, 12 , Jurga Laurencikiene 4 , Martin Krüger 5 , Matthias Blüher 8, 9 , Martin Gericke 5, 13 , Kristin Schubert 1 , Peter Kovacs 9, 14 , Rima Chakaroun 15 , Lucas Massier 9, 16
Affiliation  

Objective Human white adipose tissue (AT) is a metabolically active organ with distinct depot-specific functions. Despite their locations close to the gastrointestinal tract, mesenteric AT and epiploic AT (epiAT) have only scarcely been investigated. Here, we aim to characterise these ATs in-depth and estimate their contribution to alterations in whole-body metabolism. Design Mesenteric, epiploic, omental and abdominal subcutaneous ATs were collected from 70 patients with obesity undergoing Roux-en-Y gastric bypass surgery. The metabolically well-characterised cohort included nine subjects with insulin sensitive (IS) obesity, whose AT samples were analysed in a multiomics approach, including methylome, transcriptome and proteome along with samples from subjects with insulin resistance (IR) matched for age, sex and body mass index (n=9). Findings implying differences between AT depots in these subgroups were validated in the entire cohort (n=70) by quantitative real-time PCR. Results While mesenteric AT exhibited signatures similar to those found in the omental depot, epiAT was distinct from all other studied fat depots. Multiomics allowed clear discrimination between the IS and IR states in all tissues. The highest discriminatory power between IS and IR was seen in epiAT, where profound differences in the regulation of developmental, metabolic and inflammatory pathways were observed. Gene expression levels of key molecules involved in AT function, metabolic homeostasis and inflammation revealed significant depot-specific differences with epiAT showing the highest expression levels. Conclusion Multi-omics epiAT signatures reflect systemic IR and obesity subphenotypes distinct from other fat depots. Our data suggest a previously unrecognised role of human epiploic fat in the context of obesity, impaired insulin sensitivity and related diseases. Proteome data: ProteomeXchange Consortium via the PRIDE partner repository.59 Raw methylome outputs are available from Arrayexpress under the accession number E-MTAB-10999. Transcriptome table is available as supplementary table 7. Raw trascriptome data can be made available upon direct request to the corresponding authors.

中文翻译:

多组学揭示了与全身性胰岛素抵抗相关的人类网膜脂肪组织的独特特征

目的人类白色脂肪组织(AT)是一种代谢活跃的器官,具有不同的仓库特异性功能。尽管它们的位置靠近胃肠道,但几乎没有研究过肠系膜 AT 和网膜 AT (epiAT)。在这里,我们的目标是深入描述这些 AT,并估计它们对全身代谢改变的贡献。设计从接受 Roux-en-Y 胃旁路手术的 70 名肥胖患者收集肠系膜、网膜、网膜和腹部皮下 AT。代谢特征良好的队列包括 9 名胰岛素敏感 (IS) 肥胖受试者,他们的 AT 样本采用多组学方法进行分析,包括甲基化组、转录组和蛋白质组,以及来自年龄、性别和年龄匹配的胰岛素抵抗 (IR) 受试者的样本。体重指数(n=9)。通过定量实时 PCR 在整个队列 (n=70) 中验证了暗示这些亚组中 AT 库之间差异的发现。结果虽然肠系膜 AT 表现出与网膜库中发现的相似的特征,但 epiAT 与所有其他研究的脂肪库不同。多组学允许在所有组织中明确区分 IS 和 IR 状态。在 EpiAT 中观察到 IS 和 IR 之间的最高区分能力,其中观察到发育、代谢和炎症途径的调节存在显着差异。与 AT 功能、代谢稳态和炎症有关的关键分子的基因表达水平显示出显着的仓库特异性差异,而 epiAT 显示出最高的表达水平。结论 多组学 epiAT 特征反映了不同于其他脂肪库的全身 IR 和肥胖亚表型。我们的数据表明人类网膜脂肪在肥胖、胰岛素敏感性受损和相关疾病的背景下具有以前未被认识的作用。蛋白质组数据:ProteomeXchange Consortium,来自 PRIDE 合作伙伴存储库。59 原始甲基化组输出可从 Arrayexpress 以登录号 E-MTAB-10999 获得。转录组表可作为补充表 7 获得。原始转录组数据可根据相应作者的直接要求提供。59 原始甲基化组输出可从 Arrayexpress 以登录号 E-MTAB-10999 获得。转录组表可作为补充表 7 获得。原始转录组数据可根据相应作者的直接要求提供。59 原始甲基化组输出可从 Arrayexpress 以登录号 E-MTAB-10999 获得。转录组表可作为补充表 7 获得。原始转录组数据可根据相应作者的直接要求提供。
更新日期:2022-10-07
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