减肥手术患者血浆蛋白质组动态变化与代谢结果之间的关联

Association between plasma proteomic dynamic changes and metabolic outcomes in patients undergoing bariatric surgery.

作者信息

Diaz-Canestro Candela, Yang Wah, Chen Jiarui, Cheung Kit, Han Hao, Wang Cunchuan, Song Erfei, Lee Kwan Ming, Xue Jiang, Xu Aimin

机构信息

State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.

Department of Medicine, The University of Hong Kong, Hong Kong, China.

出版信息

Int J Obes (Lond). 2025 Jun 5. doi: 10.1038/s41366-025-01812-7.

Abstract

BACKGROUND

Bariatric surgery (BS) improves long-term glycemic control more effectively than medical treatment in patients with type 2 diabetes mellitus. The objective of this study was to explore the dynamic changes on inflammatory and metabolic-related circulating proteins in a large cohort of overweight patients and patients with class I to III obesity undergoing bariatric surgery (BS).

SUBJECTS/METHODS: We performed quantitative proteomic analysis (399 inflammatory/metabolic proteins, Olink Proteomics) in plasma samples collected before (n = 114) and 1 month (n = 67), 3 months (n = 64), 6 months (n = 60), 12 months (n = 48) and 24 months (n = 18) after either Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG).

RESULTS

Circulating proteins primarily expressed in the liver markedly changed after BS including IGFBP-1/2 (upregulated at all time points post-surgery) and the peroxisomal enzyme HAOX1 (downregulated at all time points post-surgery). Regression analysis revealed a strong association between the changes in HAOX1 and improvements in liver enzymes. In addition, a soluble broad-spectrum pattern recognition receptor, scavenger receptor cysteine rich family member with 4 domains (SSC4D), exhibited the highest decrease among all proteins at 24 months post-surgery. Finally, we detected that inflammatory markers were transiently increased after RYGB compared to VSG as well as in patients with severe obesity compared to patients with overweight and patients with obesity at 1-month post-surgery.

CONCLUSIONS

This study identified novel inflammatory and metabolic proteins possibly implicated in the systemic metabolic response to BS.

摘要

背景

在2型糖尿病患者中,减肥手术(BS)比药物治疗更有效地改善长期血糖控制。本研究的目的是探讨一大批超重患者和接受减肥手术(BS)的I至III级肥胖患者炎症和代谢相关循环蛋白的动态变化。

受试者/方法:我们对在接受Roux-en-Y胃旁路术(RYGB)或垂直袖状胃切除术(VSG)之前(n = 114)以及术后1个月(n = 67)、3个月(n = 64)、6个月(n = 60)、12个月(n = 48)和24个月(n = 18)采集的血浆样本进行了定量蛋白质组分析(399种炎症/代谢蛋白,Olink蛋白质组学)。

结果

BS术后主要在肝脏中表达的循环蛋白发生了显著变化,包括胰岛素样生长因子结合蛋白-1/2(术后所有时间点均上调)和过氧化物酶体酶HAOX1(术后所有时间点均下调)。回归分析显示HAOX1的变化与肝酶改善之间存在强关联。此外,一种可溶性广谱模式识别受体,富含半胱氨酸的清道夫受体家族成员4结构域(SSC4D),在术后24个月时在所有蛋白质中下降幅度最大。最后,我们检测到与VSG相比,RYGB术后炎症标志物短暂升高,并且与超重和肥胖患者相比,严重肥胖患者在术后1个月时炎症标志物也短暂升高。

结论

本研究确定了可能与BS全身代谢反应有关的新型炎症和代谢蛋白。

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