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

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 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.