研究显示，AT的生物力学特性与肥胖相关并发症的发展密切相关，除改善包括2型糖尿病（T2D）在内的肥胖相关代谢疾病外，减肥手术（BS）是持续减肥的最有效选择。2022年1月8日，西班牙潘普洛纳纳瓦拉大学诊所内分泌与营养系Gema Frühbeck团队在Acta Biomaterialia上发表了题为“Changes in mechanical properties of adipose tissue after bariatric surgery driven by extracellular matrix remodelling and neovascularization are associated with metabolic improvements”的研究论文。在本研究中，团队旨在确定采取BS和热量限制（CR）实现体重减轻后，其对AT生物力学特性的影响。研究揭示了BS后EWAT适应的新见解，即胶原交联和合成减少，降解增加，血管密度增加，同时提供更高的刚度和更大的延展性。
在肥胖进展期间，AT的胞外基质（ECM）经历了不断重塑和生物力学拉伸，ECM的这些改变与肥胖相关并发症病理学密切相关，包括T2D、心血管疾病或癌症，主要与缺氧反应、加速血管生成和血管化、炎症、纤维化等有关。肥胖中ECM刚度的增加主要是由于存在更厚且排列更整齐的胶原纤维，这会导致其可塑性程度降低。
脂肪硬度不仅取决于组织本身，还取决于其数量和分布。流变学研究表明，脂肪细胞周围胶原网络的变化与AT的杨氏系数（E）变化有关。单轴应变实验表明，E是特异性的，与皮下AT相比，内脏AT增加。细胞和ECM之间的相互作用是通过整合素和钙粘蛋白的跨膜细胞表面受体进行的，AT中整合素信号通路的改变与饮食诱导（DIO）肥胖动物模型中的胰岛素抵抗有关。
肥胖的发展是由生物、环境和社会经济因素等复杂相互作用导致的，这些因素会随着时间的推移持续存在能量失衡，其治疗可通过生活方式干预来实现。事实上，BS被认为是患者持续减轻体重（WL）的最有效选择，其诱导的WL已被证明可以重塑AT的ECM组成。
在本研究中，团队在构建的HFD喂养肥胖大鼠模型基础上，对其进行单次吻合十二指肠旁路袖状胃切除术（SADI-S），随后分析SADI-S对喂食ND或HFD大鼠AT的机械性能和纤维化转换影响，以及AT生物力学特性变化与ECM、炎症和机械转导相关因子的差异基因表达和蛋白质水平之间的关系，电子显微镜检查BS前后EWAT的超微结构组织。
结果证明，BS而非CR改变了肥胖大鼠模型中EWAT的生物力学特性，这与代谢改善有关。BS后EWAT中胶原和Lox基因表达水平下降，而弹性蛋白和Mmps mRNA水平升高，这也与生物力学特性有关。此外，术后，在EWAT中观察到血管密度增加，Acta2和Antxr1基因表达水平上调证实了这点，其亦与生物力学特性相关。与动物模型的EWAT相比，肥胖患者内脏AT显示出较高的刚度。
总而言之，在这项研究中，团队首次表明，AT生物力学特性在肥胖中降低，术后，可通过促进ECM重塑和新生血管形成而增加。此外，生物力学特性的这些变化与代谢稳态的改善有关。对术后AT的可塑性和生物力学特性的更好表征为开发创新策略，以减少AT中的纤维化和炎症以及更好地了解肥胖及其相关并发症开辟了一个新领域。
图 本文图形摘要示意图，反映了新陈代谢和脂肪生物学变化及其基础。
题目
Changes in mechanical properties of adipose tissue after bariatric surgery driven by extracellular matrix remodelling and neovascularization are associated with metabolic improvements
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.
研究意义：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.
关键词：Obesity; adipose tissue; extracellular matrix remodeling; biomechanical properties; bariatric surgery
