Saraswathi Viswanathan, Ai Weilun, Kumar Vikas, Sharma Kanika, Gopal Thiyagarajan, Kumar Narendra, Malhi Harmeet, Sehrawat Tejasav, Desouza Cyrus V
VA Nebraska-Western Iowa Health Care System, Omaha, NE 68105, USA.
Department of Internal Medicine, Division of Diabetes, Endocrinology, and Metabolism, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Biomedicines. 2024 Apr 3;12(4):799. doi: 10.3390/biomedicines12040799.
Circulating exosome-enriched extracellular vesicles (EVs) have drawn considerable importance in obesity-related insulin-resistance (IR). We sought to compare the proteomics profile of serum exosomes from normal individuals and those with obesity and IR.
We isolated serum exosomes from male subjects with obesity and insulin resistance (Ob-IR, HOMA-IR > 2.0) and lean/overweight insulin-sensitive (Normal (N), HOMA-IR < 2.0) individuals. The differential protein expression between the two groups was detected by a label-free quantitative mass spectrometry analysis followed by GO annotation and ingenuity pathway analysis (IPA).
We identified 23 upregulated and 46 downregulated proteins between Ob-IR and N groups. Some of these proteins are involved in altering insulin signaling (VPS13C, TBC1D32, TTR, and ADIPOQ), inflammation (NFκB and CRP), and B-cell proliferation/activation (IGLV4-69, IGKV1D-13, and IGHV4-28). GO analysis revealed that the differentially expressed proteins (DEPs) are mainly involved in regulating immune cell activation and are located in extracellular space. IPA analysis showed that top molecules mediating IR, inflammation and B-cell activation were upregulated in Ob-IR subjects compared to N subjects.
Serum exosomal proteins can be used as biomarkers to identify the future risk of diabetes and a therapeutic target to prevent or slow down the progression of diabetes in high-risk individuals.
循环中富含外泌体的细胞外囊泡（EVs）在肥胖相关的胰岛素抵抗（IR）中已引起相当大的关注。我们试图比较正常个体与肥胖及胰岛素抵抗个体血清外泌体的蛋白质组学特征。
我们从患有肥胖和胰岛素抵抗（Ob-IR，HOMA-IR>2.0）的男性受试者以及瘦/超重胰岛素敏感（正常（N），HOMA-IR<2.0）个体中分离血清外泌体。通过无标记定量质谱分析检测两组之间的差异蛋白质表达，随后进行基因本体（GO）注释和 Ingenuity 通路分析（IPA）。
我们在 Ob-IR 组和 N 组之间鉴定出 23 种上调蛋白和 46 种下调蛋白。其中一些蛋白质参与改变胰岛素信号传导（VPS13C、TBC1D32、TTR 和脂联素）、炎症（NFκB 和 CRP）以及 B 细胞增殖/激活（IGLV4-69、IGKV1D-13 和 IGHV4-28）。GO 分析显示，差异表达蛋白（DEPs）主要参与调节免疫细胞激活，且位于细胞外空间。IPA 分析表明，与 N 组受试者相比，介导 IR、炎症和 B 细胞激活的顶级分子在 Ob-IR 受试者中上调。
血清外泌体蛋白可作为生物标志物来识别未来患糖尿病的风险，并作为治疗靶点以预防或减缓高危个体糖尿病的进展。
