Faculty of Medicine (Division of Experimental Medicine), McGill University, Montreal, QC, Canada; Faculty of Dental Medicine and Oral Health Sciences, McGill University, Montreal, QC, Canada.
Faculty of Medicine (Division of Experimental Medicine), McGill University, Montreal, QC, Canada.
Matrix Biol. 2022 Apr;108:1-19. doi: 10.1016/j.matbio.2022.02.005. Epub 2022 Feb 26.
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核心调节剂，其在肥胖中的功能障碍是与体重相关的合并症（如 2 型糖尿病）的主要原因。许多细胞外基质蛋白（以基质组学为代表）在平衡脂肪组织健康和功能障碍方面发挥着关键作用。脂肪组织中不同细胞类型产生的细胞外基质成分可以调节脂肪细胞功能、组织扩张时的重塑、血管生成以及炎症，还可以在组织中形成纤维性病变。在本研究中，我们研究了人类肥胖中整个脂肪组织和脂肪细胞的基质组变化。我们进一步研究了与基因变化相关的网络和生物学途径，以及它们与 2 型糖尿病相关代谢功能障碍的发展的关联。我们使用了来自罕见体重不一致的 MZ 双胞胎队列的转录组数据和临床代谢参数。重-瘦差异基质组基因表达（Δ基质组）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、胰岛素代谢和脂质状态的变化。我们报告肥胖Δ基质组具有很高的特异性，1068 个基质组基因中有 130 个和 71 个在较重的同卵双胞胎脂肪组织和脂肪细胞中的表达发生改变。Δ基质组在脂肪组织和脂肪细胞之间存在很大差异，这反映了肥大脂肪细胞的炎症和其余组织驻留细胞的重塑活性。肥胖Δ基质组在现有证据的基础上进行了广泛的讨论，并报告了与基质组基因之间的新的显著关联；组织蛋白酶 A、组织蛋白酶 O、FAM20B 和 N-聚糖酶 1。
