Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain; Medical Engineering Laboratory, University of Navarra, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain.
Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Pamplona, Spain; Obesity and Adipobiology Group. Instituto de Investigación Sanitaria de Navarra (IdiSNA) Pamplona, Spain.
Acta Biomater. 2022 Mar 15;141:264-279. doi: 10.1016/j.actbio.2022.01.007. Epub 2022 Jan 8.
Biomechanical properties of adipose tissue (AT) are closely involved in the development of obesity-associated comorbidities. Bariatric surgery (BS) constitutes the most effective option for a sustained weight loss in addition to improving obesity-associated metabolic diseases including type 2 diabetes (T2D). We aimed to determine the impact of weight loss achieved by BS and caloric restriction (CR) on the biomechanical properties of AT. BS but not CR changed the biomechanical properties of epididymal white AT (EWAT) from a diet-induced obesity rat model, which were associated with metabolic improvements. We found decreased gene expression levels of collagens and Lox together with increased elastin and Mmps mRNA levels in EWAT after BS, which were also associated with the biomechanical properties. Moreover, an increased blood vessel density was observed in EWAT after surgery, confirmed by an upregulation of Acta2 and Antxr1 gene expression levels, which was also correlated with the biomechanical properties. Visceral AT from patients with obesity showed increased stiffness after tensile tests compared to the EWAT from the animal model. This study uncovers new insights into EWAT adaptation after BS with decreased collagen crosslink and synthesis as well as an increased degradation together with enhanced blood vessel density providing, simultaneously, higher stiffness and more ductility. STATEMENT OF SIGNIFICANCE: Biomechanical properties of the adipose tissue (AT) are closely involved in the development of obesity-associated comorbidities. In this study, we show for the first time that biomechanical properties of AT determined by E, UTS and strain at UTS are decreased in obesity, being increased after bariatric surgery by the promotion of ECM remodelling and neovascularization. Moreover, these changes in biomechanical properties are associated with improvements in metabolic homeostasis. Consistently, a better characterization of the plasticity and biomechanical properties of the AT after bariatric surgery opens up a new field for the development of innovative strategies for the reduction of fibrosis and inflammation in AT as well as to better understand obesity and its associated comorbidities.
脂肪组织 (AT) 的生物力学特性与肥胖相关合并症的发展密切相关。除了改善 2 型糖尿病 (T2D) 等肥胖相关代谢疾病外,减重手术 (BS) 是持续减肥的最有效选择。我们旨在确定 BS 和热量限制 (CR) 减轻体重对 AT 生物力学特性的影响。BS 而非 CR 改变了饮食诱导肥胖大鼠模型中附睾白色 AT (EWAT) 的生物力学特性,这与代谢改善有关。我们发现,BS 后 EWAT 中胶原蛋白和 Lox 的基因表达水平降低,弹性蛋白和 Mmps mRNA 水平升高,这也与生物力学特性有关。此外,手术后在 EWAT 中观察到血管密度增加,这通过 Acta2 和 Antxr1 基因表达水平的上调得到证实,这也与生物力学特性有关。与动物模型相比,肥胖患者的内脏 AT 在拉伸试验后表现出更高的刚性。这项研究揭示了 BS 后 EWAT 的适应的新见解,包括胶原交联和合成减少以及降解增加,同时血管密度增加,提供更高的刚性和更大的延展性。
脂肪组织 (AT) 的生物力学特性与肥胖相关合并症的发展密切相关。在这项研究中,我们首次表明,通过 E、UTS 和 UTS 应变确定的 AT 的生物力学特性在肥胖中降低,通过 ECM 重塑和新生血管形成的促进,在减重手术后增加。此外,这些生物力学特性的变化与代谢稳态的改善有关。一致地,对 BS 后 AT 的可塑性和生物力学特性的更好描述为开发减少 AT 纤维化和炎症的创新策略以及更好地理解肥胖及其相关合并症开辟了一个新领域。