# Untargeted Urinary Proteomics Uncovers Nephroprotective and Systemic Adaptations after Obesity Surgery-Induced Weight Loss

**Authors:** Pedro R. Pereira, David F. Carrageta, Bárbara Guerra-Carvalho, Patrícia C. Braga, João Pereira, Sofia S. Pereira, Mário Nora, Marta Guimarães, Anabela Rodrigues, Mariana P. Monteiro

PMC · DOI: 10.1021/acs.jproteome.5c00500 · Journal of Proteome Research · 2025-12-10

## TL;DR

Bariatric surgery-induced weight loss leads to kidney and systemic changes, revealed through urinary proteomics.

## Contribution

Identifies novel urinary proteins and pathways linked to nephroprotection and systemic adaptations after bariatric surgery.

## Key findings

- 1016 urinary proteins showed significant abundance changes after bariatric surgery.
- Proteins related to immune function, cytoskeleton, and kidney adaptation were notably altered.
- Markers of inflammation decreased while immune modulation and oxidative stress protection proteins increased.

## Abstract

Weight
loss induced by bariatric surgery (BS) has a profound impact
on several biological systems. This study aimed to identify urinary
proteins reflecting kidney and systemic adaptations to weight loss
in patients with obesity before and after BS. Urine samples from individuals
with obesity (n = 16) were collected before and two
years after BS. Untargeted high-resolution LC-MS with label-free quantification
was used to assess urinary proteome changes. Among the 2347 identified
proteins, 1016 depicted a significantly different abundance postsurgery
(p < 0.05). In particular, 54 proteins were either
upregulated (n = 42) or downregulated (n = 12) by at least 50% (≥1.5-fold). Protein functional classification
revealed associations with immune function (n = 17;
e.g., protein S100-A9, α-1-acid glycoproteins); cytoskeleton/cell
adhesion (n = 11; e.g., supervillin, ezrin, periplakin),
and kidney adaptation (n = 11; e.g., elongation factor
1-α 1, megalin, cubilin). A decrease in inflammation protein
markers (α-1-acid glycoproteins), alongside an increase in proteins
associated with immune modulation and oxidative stress protection
(dipeptidase 1, heat shock cognate 71 kDa protein) were observed.
Overall, the urinary proteome suggests changes in inflammation and
oxidative stress status, as well as in kidney function and cellular
organization succeeding BS. Our results reveal potential novel pathways
contributing to systemic modifications and nephroprotective effects
of BS-induced weight loss.

## Linked entities

- **Proteins:** S100A9 (S100 calcium binding protein A9), FHL2 (four and a half LIM domains 2), EVPL (envoplakin), Lrp2 (low density lipoprotein receptor-related protein 2), Cubn (Cubilin)
- **Diseases:** obesity (MONDO:0011122)

## Full-text entities

- **Genes:** CUBN (cubilin) [NCBI Gene 8029] {aka IFCR, IGS, IGS1, MGA1, gp280}, HSPA8 (heat shock protein family A (Hsp70) member 8) [NCBI Gene 3312] {aka HEL-33, HEL-S-72p, HSC54, HSC70, HSC71, HSP71}, PPL (periplakin) [NCBI Gene 5493], LRP2 (LDL receptor related protein 2) [NCBI Gene 4036] {aka DBS, GP330, LRP-2}, EEF1A1 (eukaryotic translation elongation factor 1 alpha 1) [NCBI Gene 1915] {aka CCS-3, CCS3, EE1A1, EEF-1, EEF1A, EF-Tu}, SVIL (supervillin) [NCBI Gene 6840] {aka MFM10}, S100A9 (S100 calcium binding protein A9) [NCBI Gene 6280] {aka 60B8AG, CAGB, CFAG, CGLB, L1AG, LIAG}, DPEP1 (dipeptidase 1) [NCBI Gene 1800] {aka MBD1, MDP, RDP}, EZR (ezrin) [NCBI Gene 7430] {aka CVIL, CVL, HEL-S-105, VIL2}
- **Diseases:** Weight Loss (MESH:D015431), inflammation (MESH:D007249), Obesity (MESH:D009765)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12818830/full.md

## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12818830/full.md

## References

83 references — full list in the complete paper: https://tomesphere.com/paper/PMC12818830/full.md

---
Source: https://tomesphere.com/paper/PMC12818830