Proteomic profiling reveals alterations in metabolic and cellular pathways in severe obesity and following metabolic bariatric surgery.

Abstract

In this study, we investigated the impact of bariatric surgery on the adipose proteome to better understand the metabolic and cellular mechanisms underlying weight loss following the procedure. A total of 46 patients with severe obesity were included, with samples collected both before and after bariatric surgery. In addition, 15 healthy individuals without obesity who did not undergo surgery served as controls and were studied once. We utilized quantitative liquid chromatography-tandem mass spectrometry analysis to conduct a large-scale proteomic study on abdominal subcutaneous biopsies obtained from the study participants. Our proteomic profiling revealed that among the 2,254 compared proteins, 46 were upregulated and 34 were downregulated 6 months post surgery compared with baseline [false discovery rate (FDR) < 0.01]. We observed a downregulation of proteins associated with mitochondrial integrity, amino acid catabolism, and lipid metabolism in the patients with severe obesity compared with the controls. Bariatric surgery was associated with an upregulation in pathways related to mitochondrial function, protein synthesis, folding and trafficking, actin cytoskeleton regulation, and DNA binding and repair. These findings emphasize the significant changes in metabolic and cellular pathways following bariatric surgery, highlighting the potential mechanisms underlying the observed health improvements postbariatric surgery. The data provided alongside this paper will serve as a valuable resource for the development of targeted therapeutic strategies for obesity and related metabolic complications. ClinicalTrials.gov registration numbers: NCT00793143 (registered on 19 November 2008) (https://clinicaltrials.gov/ct2/show/NCT00793143) and NCT01373892 (registered on 15 June 2011) (https://clinicaltrials.gov/ct2/show/NCT01373892).NEW & NOTEWORTHY Our study investigates the effects of metabolic bariatric surgery on adipose tissue proteins, highlighting the mechanisms driving weight loss postsurgery. Through extensive proteomic analysis of adipose biopsies from patients with severe obesity pre- and postsurgery, alongside healthy subjects without obesity, we identified significant alterations in metabolic pathways. These findings provide insights into potential therapeutic targets for obesity-related complications.