Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research (UFZ), Leipzig, Germany.
Department for Internal Medicine, Neurology and Dermatology, University Hospital Leipzig, Leipzig, Germany.
Gut. 2022 Nov;71(11):2179-2193. doi: 10.1136/gutjnl-2021-324603. Epub 2021 Oct 1.
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.
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.
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.
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.
人类白色脂肪组织（AT）是一种具有独特储存部位特异性功能的代谢活跃器官。尽管它们位于胃肠道附近，但肠系膜 AT 和网膜 AT（epiAT）的研究甚少。在这里，我们旨在深入研究这些 AT，并估计它们对全身代谢变化的贡献。
从 70 名接受 Roux-en-Y 胃旁路手术的肥胖患者中收集肠系膜、网膜、大网膜和腹部皮下 AT。代谢特征良好的队列包括 9 名胰岛素敏感（IS）肥胖患者，对其 AT 样本进行了多组学分析，包括甲基组、转录组和蛋白质组，以及与年龄、性别和体重指数匹配的胰岛素抵抗（IR）患者的样本（n=9）。在整个队列（n=70）中通过定量实时 PCR 验证了这些亚组中暗示 AT 储器之间存在差异的发现。
虽然肠系膜 AT 表现出与大网膜储器中发现的特征相似，但 epiAT 与所有其他研究的脂肪储器不同。多组学允许在所有组织中清楚地区分 IS 和 IR 状态。在 epiAT 中观察到 IS 和 IR 之间的最高区分能力，在那里观察到发育、代谢和炎症途径的调节存在明显差异。涉及 AT 功能、代谢稳态和炎症的关键分子的基因表达水平显示出明显的储存部位特异性差异，epiAT 显示出最高的表达水平。
多组学 epiAT 特征反映了全身 IR 和肥胖亚表型，与其他脂肪储器不同。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到的作用。
