Quantitative proteomics identifies plasma protein alterations that associate with metabolic and thrombotic profile changes after bariatric surgery.

Roux-en-Y gastric bypass (RYGB) surgery has been shown to lead to favourable health outcomes in obese patients. However, the molecular changes that occur and how they relate to clinical measures are poorly understood. Here, we characterise the proteomic alterations that occur in plasma of RYGB patients before and 9 months after surgery using quantitative proteomics. Plasma proteomics was performed by sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS) to identify and quantify differentially abundant proteins. Relationships between significantly altered proteins and clinical markers were examined. A gene set enrichment analysis was also conducted to identify altered pathways. From the proteomic analysis, 27 proteins increased, and 43 proteins decreased in abundance 9 months after surgery, providing insights into the physiological changes that accompany weight loss. Proteins including sex hormone binding globulin (SHBG), inter-alpha-trypsin inhibitor heavy chain 3 (ITIH3) and apolipoprotein D (APOD), which increased in abundance post-surgery, highlight improvements in lipid regulation, insulin sensitivity and inflammation. Proteins involved in coagulation, including α2-macroglobulin, kallikrein-B1, prothrombin, and factor (FX, FXI and FXII), exhibited reduced levels, aligning with a decrease in thrombotic potential. These findings provide a mechanistic understanding of how bariatric surgery leads to systemic changes in metabolic and haemostatic pathways, thus favourably modulating the risk of developing cardiovascular disease.