Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Central European Institute of Technology, Masaryk University, Brno, Czech Republic.
Am J Physiol Endocrinol Metab. 2023 Nov 1;325(5):E562-E580. doi: 10.1152/ajpendo.00153.2023. Epub 2023 Oct 4.
In this study, we aimed to comprehensively characterize the proteomic landscapes of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) in patients with severe obesity, to establish their associations with clinical characteristics, and to identify potential serum protein biomarkers indicative of tissue-specific alterations or metabolic states. We conducted a cross-sectional analysis of 32 patients with severe obesity (16 males and 16 females) of Central European descent who underwent bariatric surgery. Clinical parameters and body composition were assessed using dual-energy X-ray absorptiometry (DXA) and bioelectrical impedance, with 15 patients diagnosed with type 2 diabetes (T2D) and 17 with hypertension. Paired SAT and VAT samples, along with serum samples, were subjected to state-of-the-art proteomics liquid chromatography-mass spectrometry (LC-MS). Our analysis identified 7,284 proteins across SAT and VAT, with 1,249 differentially expressed proteins between the tissues and 1,206 proteins identified in serum. Correlation analyses between differential protein expression and clinical traits suggest a significant role of SAT in the pathogenesis of obesity and related metabolic complications. Specifically, the SAT proteomic profile revealed marked alterations in metabolic pathways and processes contributing to tissue fibrosis and inflammation. Although we do not establish a definitive causal relationship, it appears that VAT might respond to SAT metabolic dysfunction by potentially enhancing mitochondrial activity and expanding its capacity. However, when this adaptive response is exceeded, it could possibly contribute to insulin resistance (IR) and in some cases, it may be associated with the progression to T2D. Our findings provide critical insights into the molecular foundations of SAT and VAT in obesity and may inform the development of targeted therapeutic strategies. This study provides insights into distinct proteomic profiles of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and serum in patients with severe obesity and their associations with clinical traits and body composition. It underscores SAT's crucial role in obesity development and related complications, such as insulin resistance (IR) and type 2 diabetes (T2D). Our findings emphasize the importance of understanding the SAT and VAT balance in energy homeostasis, proteostasis, and the potential role of SAT capacity in the development of metabolic disorders.
在这项研究中，我们旨在全面描绘严重肥胖患者皮下脂肪组织（SAT）和内脏脂肪组织（VAT）的蛋白质组学特征，建立它们与临床特征的关联，并识别潜在的血清蛋白生物标志物，以指示组织特异性改变或代谢状态。我们对 32 名中欧裔严重肥胖患者（16 名男性和 16 名女性）进行了横断面分析，这些患者接受了减肥手术。使用双能 X 射线吸收法（DXA）和生物电阻抗法评估临床参数和身体成分，其中 15 名患者被诊断为 2 型糖尿病（T2D），17 名患者患有高血压。对配对的 SAT 和 VAT 样本以及血清样本进行了最先进的蛋白质组学液相色谱-质谱（LC-MS）分析。我们的分析在 SAT 和 VAT 中鉴定了 7284 种蛋白质，其中 1249 种蛋白质在组织之间差异表达，1206 种蛋白质在血清中鉴定。差异蛋白表达与临床特征之间的相关性分析表明，SAT 在肥胖及其相关代谢并发症的发病机制中具有重要作用。具体而言，SAT 的蛋白质组谱显示代谢途径和过程发生了明显改变，这些改变与组织纤维化和炎症有关。尽管我们没有建立明确的因果关系，但似乎 VAT 通过潜在地增强线粒体活性和扩大其容量来对 SAT 的代谢功能障碍做出反应。然而，当这种适应性反应超出时，它可能有助于胰岛素抵抗（IR），并且在某些情况下，它可能与向 2 型糖尿病的进展有关。我们的研究结果为肥胖症中 SAT 和 VAT 的分子基础提供了重要的见解，并可能为靶向治疗策略的发展提供信息。本研究提供了关于严重肥胖患者皮下脂肪组织（SAT）、内脏脂肪组织（VAT）和血清的不同蛋白质组学特征及其与临床特征和身体成分的关联的见解。它强调了 SAT 在肥胖发展和相关并发症（如胰岛素抵抗（IR）和 2 型糖尿病（T2D））中的关键作用。我们的研究结果强调了理解 SAT 和 VAT 在能量平衡、蛋白质平衡中的平衡以及 SAT 容量在代谢紊乱发展中的潜在作用的重要性。
