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Bariatric Surgery

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

International Journal of Obesity volume 49, pages 1745–1754 (2025)Cite this article

Subjects

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.

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Fig. 1: Proteomic changes in response to bariatric surgery.
Fig. 2: Longitudinal trajectories of proteomic changes in response to bariatric surgery.
Fig. 3: Gene set enrichment analysis for proteins altered after bariatric surgery.
Fig. 4: Longitudinal trajectories of proteomic changes in response to bariatric surgery according to type of surgery, sex and obesity status at baseline.
Fig. 5: Proteomic changes associated with metabolic outcomes in response to bariatric surgery.

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Data availability

Olink raw proteomics data is provided in Table S1. Olink proteomics data (mean and SD) for all the proteins at different time points is provided in Table S2. This study reports original code deposited at (https://github.com/Cclarrisacheung/ijo-candeladiazcanestro-bariatric-surgery-2025). Any additional information required to reanalyze the data reported in this work paper is available from the lead contact upon request.

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Funding

This work was supported by Hong Kong Research Grants Council/Area of Excellence (AoE/M/707-18) and General Research Fund (17117320 and 17121523); Shenzhen-Hong Kong-Macau Science and Technology Program (Category C, SGDX20210823103537031); Hong Kong Health and Medical Research Fund (08192316), and National Natural Science Foundation of China (82161138026).

Author information

Author notes

  1. These authors contributed equally: Candela Diaz-Canestro, Wah Yang.

Authors and Affiliations

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

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

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

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

  3. Center for Molecular Cardiology, University of Zurich, Schlieren, Switzerland

    Candela Diaz-Canestro & Kit Cheung

  4. Department of Metabolic and Bariatric Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, China

    Wah Yang & Cunchuan Wang

  5. Guangdong-Hong Kong Joint Institute for Metabolic Medicine, The University of Hong Kong, Hong Kong, China

    Hao Han, Cunchuan Wang, Erfei Song, Kwan Ming Lee, Jiang Xue & Aimin Xu

Authors
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Contributions

CD-C performed bioinformatics analysis, interpreted results, and wrote the manuscript. WY collected patients’ data. JC and KC performed bioinformatics analysis. HH, DL and JX performed Olink proteomics. CW and ES contributed to the acquisition of data. AX conceived and supervised the study and wrote and edited the manuscript. CD-C, and AX revised the manuscript critically for important intellectual contents.

Corresponding author

Correspondence to Aimin Xu.

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Diaz-Canestro, C., Yang, W., Chen, J. et al. Association between plasma proteomic dynamic changes and metabolic outcomes in patients undergoing bariatric surgery. Int J Obes 49, 1745–1754 (2025). https://doi.org/10.1038/s41366-025-01812-7

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