Li Yi, Yang Huawu, Zhang Xinpeng, He Xingyu, Liuli Anke, Li Rui, Han Xingyu, Li Yongmei, Gao Pan
Department of Radiology, The Third People's Hospital of Chengdu, Chengdu, Sichuan, China.
Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Front Endocrinol (Lausanne). 2025 Jul 31;16:1625501. doi: 10.3389/fendo.2025.1625501. eCollection 2025.
Adipose tissue remodeling induced by bariatric surgery plays a pivotal role in promoting weight loss and metabolic improvement. However, the underlying molecular mechanisms, particularly protein-metabolite regulatory networks, remain poorly understood. This integrative proteomic and metabolomic study identifies key pathway alterations and molecular signatures associated with metabolic phenotypes, offering novel mechanistic insights into the therapeutic efficacy of bariatric surgery.
Visceral adipose tissue samples were analyzed using label-free DIA quantitative proteomics and LC-MS/MS metabolomics. Proteomic and metabolomic data were processed with MaxQuant software and XCMS R package, respectively.
Proteomic and metabolomic analyses were performed on visceral adipose tissue from 10 obese patients undergoing sleeve gastrectomy and 10 controls. Proteomic profiling quantified identified 135 differentially expressed proteins (57 upregulated, 78 downregulated), with PHACTR2 and PLIN2 upregulated in obesity and ADAR down-regulated in obesity. Enrichment analyses indicated disruptions in lipid droplet formation, muscle processes, and protein autophosphorylation, with KRT1/MYH9 and NF1/ATR identified as hub proteins. Metabolomics revealed 191 differential metabolites (110 upregulated, 81 downregulated), with 4-Vinylcyclohexene positively correlated with BMI and asparagine-betaxanthin negatively correlated. KEGG analysis showed disturbances in purine/pyrimidine metabolism, AMPK signaling, and cortisol biosynthesis. Integrated protein-metabolite network analysis identified OSBPL10, CUL2, and PRTN3 as potential regulators of lipid metabolism and insulin resistance, offering insights into obesity-associated metabolic dysfunction.
This study integrated proteomic and metabolomic data from visceral adipose tissue obtained through sleeve gastrectomy, identifying obesity-related functional pathways and molecular signatures linked to metabolic phenotypes, highlighting the value of multi-omics in understanding adipose tissue remodeling and postoperative metabolic improvement.
减肥手术诱导的脂肪组织重塑在促进体重减轻和代谢改善方面起着关键作用。然而，其潜在的分子机制，尤其是蛋白质-代谢物调控网络，仍知之甚少。这项蛋白质组学和代谢组学的综合研究确定了与代谢表型相关的关键通路改变和分子特征，为减肥手术的治疗效果提供了新的机制见解。
使用无标记DIA定量蛋白质组学和LC-MS/MS代谢组学分析内脏脂肪组织样本。蛋白质组学和代谢组学数据分别用MaxQuant软件和XCMS R包进行处理。
对10例接受袖状胃切除术的肥胖患者和10例对照者的内脏脂肪组织进行了蛋白质组学和代谢组学分析。蛋白质组分析定量鉴定出135种差异表达蛋白（57种上调，78种下调），其中PHACTR2和PLIN2在肥胖中上调，ADAR在肥胖中下调。富集分析表明脂滴形成、肌肉过程和蛋白质自磷酸化受到破坏，KRT1/MYH9和NF1/ATR被确定为枢纽蛋白。代谢组学揭示了191种差异代谢物（110种上调，81种下调），4-乙烯基环己烯与BMI呈正相关，天冬酰胺-甜菜黄素呈负相关。KEGG分析显示嘌呤/嘧啶代谢、AMPK信号通路和皮质醇生物合成受到干扰。综合蛋白质-代谢物网络分析确定OSBPL10、CUL2和PRTN3为脂质代谢和胰岛素抵抗的潜在调节因子，为肥胖相关代谢功能障碍提供了见解。
本研究整合了通过袖状胃切除术获得的内脏脂肪组织的蛋白质组学和代谢组学数据，确定了与代谢表型相关的肥胖相关功能通路和分子特征，突出了多组学在理解脂肪组织重塑和术后代谢改善方面的价值。
