Institute of Medicine, Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
Wallenberg Centre for Molecular and Translational Medicine, Sahlgrenska Academy, University of Gothenburg, 405 30 Gothenburg, Sweden.
Int J Mol Sci. 2022 Jan 4;23(1):520. doi: 10.3390/ijms23010520.
Obesity is associated with extensive expansion and remodeling of the adipose tissue architecture, including its microenvironment and extracellular matrix (ECM). Although obesity has been reported to induce adipose tissue fibrosis, the composition of the ECM under healthy physiological conditions has remained underexplored and debated. Here, we used a combination of three established techniques (picrosirius red staining, a colorimetric hydroxyproline assay, and sensitive gene expression measurements) to evaluate the status of the ECM in metabolically healthy lean (MHL) and metabolically unhealthy obese (MUO) subjects. We investigated ECM deposition in the two major human adipose tissues, namely the omental and subcutaneous depots. Biopsies were obtained from the same anatomic region of respective individuals. We found robust ECM deposition in MHL subjects, which correlated with high expression of collagens and enzymes involved in ECM remodeling. In contrast, MUO individuals showed lower expression of ECM components but elevated levels of ECM cross-linking and adhesion proteins, e.g., lysyl oxidase and thrombospondin. Our data suggests that subcutaneous fat is more prone to express proteins involved in ECM remodeling than omental adipose tissues. We conclude that a more dynamic ability to deposit and remodel ECM may be a key signature of healthy adipose tissue, and that subcutaneous fat may adapt more readily to changing metabolic conditions than omental fat.
肥胖与脂肪组织结构的广泛扩张和重塑有关,包括其微环境和细胞外基质(ECM)。尽管已经报道肥胖会引起脂肪组织纤维化,但健康生理条件下 ECM 的组成仍未得到充分探索和争论。在这里,我们使用了三种已建立的技术(苦味酸天狼星红染色、比色羟脯氨酸测定法和敏感的基因表达测量)的组合,来评估代谢健康的瘦(MHL)和代谢不健康的肥胖(MUO)受试者的 ECM 状态。我们研究了两种主要的人体脂肪组织,即网膜和皮下脂肪组织中的 ECM 沉积。从各自个体的相同解剖区域获取活检。我们发现 MHL 受试者中存在大量的 ECM 沉积,这与胶原蛋白和参与 ECM 重塑的酶的高表达有关。相比之下,MUO 个体表现出 ECM 成分表达较低,但 ECM 交联和粘附蛋白(例如赖氨酰氧化酶和血栓素)水平升高。我们的数据表明,与网膜脂肪组织相比,皮下脂肪更倾向于表达参与 ECM 重塑的蛋白。我们得出结论,更具活力的 ECM 沉积和重塑能力可能是健康脂肪组织的一个关键特征,并且皮下脂肪可能比网膜脂肪更容易适应代谢变化的条件。