Integration of Proteomic and Lipidomic Analysis Reveals Potential Markers of Insulin Resistance in Young Children With Obesity.

IF 5.6 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Pediatric Diabetes Pub Date : 2025-10-10 eCollection Date: 2025-01-01 DOI:10.1155/pedi/9918136

Lujie Liu, Jing Zhou, Shuang Guo, Biyao Lian, Hongai Zhang, Yanying Dong, Yuesheng Liu, Shunming Zhang, Chunyan Yin

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Abstract

Objective: This study aimed to identify novel proteomic and lipidomic biomarkers of insulin resistance (IR) in young children with obesity and to assess the ability of hub lipids and proteins in the diagnosis of IR.

Methods: The discovery cohort consisted of 50 prepubertal children, including 30 children with obesity and 20 lean. The validation cohort included 25 children with obesity and IR (obese-IR) and 25 children with obesity without IR (obese-NIR). Fasting plasma was collected from all participants for Olink proteomics and untargeted lipidomics. Pearson correlation analysis was used to identify proteins and lipids associated with IR, and area under the receiver operating characteristic (AUROC) was applied to compare the ability of the identified proteins and lipids with traditional indices in the diagnosis of IR.

Results: In the discovery cohort, a total of 15 lipids and 10 proteins had significant correlation with IR. In the validation cohort, protein fatty acid binding protein 4 (FABP4) and gene serpin family E member 1 (PAI) were overexpressed in obese-IR children compared to obese-NIR children, while insulin like growth factor binding protein 1 (IGFBP-1) and paraoxonase 3 (PON3) were lower in the IR group than in the obese-NIR group; five lipids including sphingosine (d16:0), coenzyme (Q8), ceramides phosphate (d42:2), phosphatidylethanolamine (37:2e), and phosphatidylcholine (18:1e_16:0), showed significant (p < 0.05) change in obese-IR children compared to obese-NIR children. In addition, the AUC-ROC was 0.89 for IGFBP-1, 0.81 for PON3, and 0.65 for PAI. The ability of IGFBP-1, PON3, and PAI to diagnose IR was better than that of adiponectin and leptin. The AUROC of phosphatidylcholine (18:1e_16:0) and coenzyme (Q8) were 0.80 and 0.73, respectively, which was significantly higher than the AUROC of triglycerides(TGs), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C).

Conclusion: Proteomic and lipidomic analysis can allow for the identification of potential new candidate biomarkers for IR. The ability of novel biomarkers to diagnose IR was better than traditional indicators.

Trial registration: Chinese Clinical Trial Registry: ChiCTR2300072179.

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结合蛋白质组学和脂质组学分析揭示了幼儿肥胖患者胰岛素抵抗的潜在标志物。

目的：本研究旨在鉴定年幼肥胖儿童胰岛素抵抗（IR）的新的蛋白质组学和脂质组学生物标志物，并评估中枢脂质和蛋白质在IR诊断中的能力。方法：发现队列包括50名青春期前儿童，其中肥胖儿童30名，瘦弱儿童20名。验证队列包括25名肥胖合并IR的儿童（obesity -IR）和25名无IR的肥胖儿童（obesity - nir）。收集所有参与者的空腹血浆进行Olink蛋白质组学和非靶向脂质组学。采用Pearson相关分析鉴定与IR相关的蛋白和脂质，并采用受试者工作特征面积（area under the receiver operating characteristic， AUROC）比较鉴定的蛋白和脂质与传统指标诊断IR的能力。结果：在发现队列中，共有15种脂质和10种蛋白与IR有显著相关性。在验证队列中，与肥胖- nir儿童相比，肥胖-IR儿童中蛋白质脂肪酸结合蛋白4 （FABP4）和基因丝氨酸蛋白家族E成员1 （PAI）过表达，而胰岛素样生长因子结合蛋白1 （IGFBP-1）和对氧磷酶3 （PON3）在IR组中低于肥胖- nir组；5种脂质，包括鞘磷脂（d16:0）、辅酶（Q8）、磷酸神经酰胺（d42:2）、磷脂酰乙醇胺（37:2）和磷脂酰胆碱（18:1e_16:0），在肥胖- ir儿童中与肥胖- nir儿童相比有显著（p < 0.05）的变化。此外，IGFBP-1的AUC-ROC为0.89，PON3为0.81，PAI为0.65。IGFBP-1、PON3和PAI对IR的诊断能力优于脂联素和瘦素。磷脂酰胆碱（18:1e_16:0）和辅酶（Q8）的AUROC分别为0.80和0.73，显著高于甘油三酯（tg）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）的AUROC。结论：蛋白质组学和脂质组学分析可用于鉴定潜在的新的候选IR生物标志物。新型生物标志物诊断IR的能力优于传统指标。试验注册：中国临床试验注册中心：ChiCTR2300072179。

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来源期刊

Pediatric Diabetes 医学-内分泌学与代谢

CiteScore

6.60

自引率

14.70%

发文量

141

审稿时长

4-8 weeks

期刊介绍： Pediatric Diabetes is a bi-monthly journal devoted to disseminating new knowledge relating to the epidemiology, etiology, pathogenesis, management, complications and prevention of diabetes in childhood and adolescence. The aim of the journal is to become the leading vehicle for international dissemination of research and practice relating to diabetes in youth. Papers are considered for publication based on the rigor of scientific approach, novelty, and importance for understanding mechanisms involved in the epidemiology and etiology of this disease, especially its molecular, biochemical and physiological aspects. Work relating to the clinical presentation, course, management and outcome of diabetes, including its physical and emotional sequelae, is considered. In vitro studies using animal or human tissues, whole animal and clinical studies in humans are also considered. The journal reviews full-length papers, preliminary communications with important new information, clinical reports, and reviews of major topics. Invited editorials, commentaries, and perspectives are a regular feature. The editors, based in the USA, Europe, and Australasia, maintain regular communications to assure rapid turnaround time of submitted manuscripts.