Proteomic Signatures of Adiposomes Track Cardiometabolic Risk Reduction Following Bariatric Surgery.

Adipose tissue-derived extracellular vesicles (adiposomes) carry a protein cargo that we previously showed differs between obese and lean individuals. In this study, we investigate how adiposomal protein cargo changes in response to sleeve gastrectomy and examine whether these changes are associated with clinical improvements. Twenty-three obese adults underwent pre- and post-bariatric surgery adipose sampling for adiposome isolation and clinical assessments that included vascular and metabolic profiles and inflammatory markers. The adiposomal protein cargo was analyzed via non-targeted proteomics. Differential protein abundance, pathway enrichment, and correlation analyses were assessed. Twelve weeks after bariatric surgery, BMI and fat mass decreased, accompanied by improved glucose and lipid profiles. Inflammatory markers (leptin, IL-6, CRP) also declined, while adiponectin and nitric oxide increased. Adiposomal proteomics identified 287 proteins, with 138 significantly altered. Downregulated proteins included PRDX2, FN1, SERPIND1, and inflammatory mediators; upregulated proteins included talin-1, fibrinogens, and adiponectin. Correlation analysis linked these changes to improvements in lipid profiles, vascular function, and circulating inflammatory markers. Pathway analysis revealed inhibition of lipid-regulatory pathways alongside enrichment of immune, metabolic, and vascular pathways, including lipoprotein metabolism and endothelial signaling. Bariatric surgery-induced cardiometabolic improvements were accompanied by adiposome proteomic remodeling, characterized by reduced inflammation and metabolic reprogramming.