Departament de Medicina i Cirurgia, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili (URV), 43201 Reus, Spain.
GEMMAIR Research Group, Institut d'Investigació Sanitària Pere Virgili (IISPV), 43005 Tarragona, Spain.
J Proteomics. 2025 Jan 6;310:105317. doi: 10.1016/j.jprot.2024.105317. Epub 2024 Sep 21.
In this study, we aimed to evaluate circulating proteomic levels in women with morbid obesity (MO) compared to normal-weight (NW) women. Moreover, we have compared the proteomic profile between women with metabolically healthy (MH) MO and those with type 2 diabetes mellitus (T2DM). The study included 66 normal-weight (NW) women and 129 women with MO (54 MH and 75 with T2DM). Blood samples were processed for proteomics, involving protein extraction, quantification, digestion with peptide labelling and Nano (liquid chromatography (LC)-(Orbitrap) coupled to mass/mass spectrometry (MS/MS) analysis. Statistical analyses were performed. We identified 257 proteins. Women with MO showed significantly increased levels of 35 proteins and decreased levels of 45 proteins compared to NW women. Enrichment analysis of metabolic pathways revealed significant findings. Women with MO have an altered proteomic profile compared to normal-weight women, involving proteins significantly related to chylomicron assembly, complement cascade, clotting pathways and the insulin growth factor system. Regarding women with MO and T2DM compared to MHMO women, the proteomic profile shows alterations in mostly the same pathways associated with obesity. These findings confirmed in previous reports can help us better understand the pathophysiology of obesity and associated diseases. SIGNIFICANCE: Women with morbid obesity (MO) exhibit substantial proteomic alterations compared to normal-weight (NW) women, involving 80 proteins. These alterations are linked to significant metabolic pathways, including chylomicron assembly, complement cascade, clotting pathways and the insulin growth factor system. Additionally, women with MO and type 2 diabetes mellitus (T2DM) compared to metabolically healthy MO women share similar proteomic changes than the first comparison. These findings enhance our understanding of the pathophysiology of obesity and associated diseases, offering potential targets for therapeutic intervention.
在这项研究中，我们旨在评估病态肥胖 (MO) 女性与正常体重 (NW) 女性相比的循环蛋白质组水平。此外，我们比较了代谢健康 (MH) MO 女性和 2 型糖尿病 (T2DM) 女性之间的蛋白质组谱。该研究包括 66 名正常体重 (NW) 女性和 129 名 MO 女性 (54 名 MH 和 75 名 T2DM)。处理血液样本进行蛋白质组学分析，包括蛋白质提取、定量、肽标记消化和纳升 (液相色谱 (LC)-(Orbitrap) 与质谱/质谱 (MS/MS) 分析。进行了统计分析。我们鉴定了 257 种蛋白质。与 NW 女性相比，MO 女性表现出 35 种蛋白质水平显著升高和 45 种蛋白质水平显著降低。代谢途径的富集分析显示出显著的发现。与正常体重女性相比，MO 女性的蛋白质组谱发生了改变，涉及与乳糜微粒组装、补体级联、凝血途径和胰岛素生长因子系统显著相关的蛋白质。关于 MO 和 T2DM 女性与 MHMO 女性相比，蛋白质组谱显示与肥胖相关的相同途径发生了改变。这些在以前的报告中得到证实的发现可以帮助我们更好地理解肥胖和相关疾病的病理生理学。意义：与正常体重 (NW) 女性相比，病态肥胖 (MO) 女性表现出大量蛋白质组学改变，涉及 80 种蛋白质。这些改变与重要的代谢途径有关，包括乳糜微粒组装、补体级联、凝血途径和胰岛素生长因子系统。此外，与代谢健康 MO 女性相比，MO 和 2 型糖尿病 (T2DM) 女性具有相似的蛋白质组变化。这些发现增强了我们对肥胖和相关疾病病理生理学的理解，为治疗干预提供了潜在靶点。
