Bariatric surgery (BS) remains the most effective strategy for treating obesity, offering notable improvements in cardiometabolic health and promoting remission of type 2 diabetes. The majority of post-surgical fat loss occurs in the subcutaneous adipose tissue (SAT), yet the functional changes within this depot and its precise role in the benefits of BS are still debated. To explore alterations in protein expression and associated molecular pathways in abdominal SAT (aSAT) following weight normalization induced by BS, we applied a proteomic strategy using sequential window acquisition of all theoretical mass spectra (SWATH-MS), complemented with Western blot, electron microscopy, and RT-qPCR analyses. Our study revealed that BS upregulated proteins involved in energy metabolism, the citric acid cycle, respiratory electron transport, triglyceride breakdown, ATP generation, pyruvate metabolism, glycolysis/gluconeogenesis, and thermogenic processes. Conversely, proteins associated with immune-related pathways were downregulated. We also observed that obesity led to reduced mitochondrial density and coverage in SAT, a defect that BS effectively reversed. These findings uncover specific proteins, genes, and molecular mechanisms that contribute to improved adipose tissue function after BS, including diminished inflammation, enhanced glucose uptake, increased insulin sensitivity, elevated de novo lipogenesis, improved mitochondrial performance, and smaller adipocyte size.
