Adipose tissue is a central regulator of metabolic health and its failure in obesity is a major cause of weight associated comorbidities, such as type 2 diabetes. Many extracellular matrix proteins, represented by matrisome, play a critical role in balancing adipose tissue health and dysfunction. Extracellular matrix components, produced by different cell types of adipose tissue, can modulate adipocyte function, tissue remodeling during expansion, angiogenesis, and inflammation and also form fibrotic lesions in the tissue. In this study, we investigated changes in matrisome of whole adipose tissue and adipocytes in human obesity. We investigated further the networks and biological pathways of the genes related to the changes and their association to development of metabolic dysfunction linked to type 2 diabetes. We used transcriptome data and clinical metabolic parameters from a rare weight-discordant MZ twin cohort. The Heavy-Lean differential matrisome gene expression (Δmatrisome) and differential metabolic parameters reflect changes in adipose tissue upon weight gain and changes in whole body glucose, insulin metabolism, as well as lipid status. We report that obesity Δmatrisome shows high specificity with 130 and 71 of the 1068 matrisome genes showing altered expression in the adipose tissue and adipocytes of heavier co-twin, respectively. The Δmatrisome differs considerably between adipose tissue vs adipocytes which reflects inflammation of hypertrophic adipocytes and the remodeling activity of the rest of the tissue resident cells. The obesity Δmatrisome is discussed extensively in the light of existing evidence and novel significant associations to obesity are reported to matrisome genes; cathepsin A, cathepsin O, FAM20B and N-glycanase1.

脂肪组织是代谢健康的中枢调节剂，它在肥胖方面的失败是导致体重相关合并症（如 2 型糖尿病）的主要原因。许多以基质体为代表的细胞外基质蛋白在平衡脂肪组织健康和功能障碍方面发挥着关键作用。由不同细胞类型的脂肪组织产生的细胞外基质成分可以调节脂肪细胞功能、扩张过程中的组织重塑、血管生成和炎症，并在组织中形成纤维化损伤。在这项研究中，我们调查了人类肥胖症中整个脂肪组织和脂肪细胞的基质体的变化。我们进一步研究了与这些变化相关的基因的网络和生物学途径，以及它们与与 2 型糖尿病相关的代谢功能障碍发展的关联。我们使用了来自罕见的体重不一致 MZ 双胞胎队列的转录组数据和临床代谢参数。重瘦差异基质体基因表达（Δmatrisome）和差异代谢参数反映了体重增加时脂肪组织的变化以及全身葡萄糖、胰岛素代谢以及脂质状态的变化。我们报告肥胖 Δmatrisome 显示出高特异性，1068 个基质体基因中的 130 个和 71 个基因分别在较重的双胞胎的脂肪组织和脂肪细胞中表现出改变的表达。脂肪组织与脂肪细胞之间的 Δmatrisome 差异很大，这反映了肥大脂肪细胞的炎症和其他组织驻留细胞的重塑活性。根据现有证据，肥胖 Δmatrisome 得到了广泛的讨论，据报道，肥胖与肥胖的新显着关联与 matrisome 基因有关；组织蛋白酶 A、组织蛋白酶 O、FAM20B 和 N-聚糖酶 1。