Adipose tissue transcriptome before and after surgery: effects on genes driving lipid metabolism, inflammation, and RNA processing

Abstract Aims Obesity, marked by excess adipose tissue, is strongly associated with increased cardiometabolic risk. Metabolic bariatric surgery (MBS) leads to significant and sustained weight loss and improves metabolic profiles in persons with severe obesity. However, how MBS induces persistent transcriptional changes in adipose tissue and their contributions to cardiometabolic improvements remain unclear. This study examined subcutaneous (SAT) and visceral (VAT) adipose tissue transcriptome profiles in people with severe obesity, tracking changes in SAT after MBS, with a focus on lipid metabolism, inflammation, RNA processing, and cholesterol handling. Methods This study included 42 women with severe obesity undergoing MBS and 15 sex-matched healthy people without obesity as controls. Targeted RNA expression profiling was performed on SAT and VAT samples. Results In people with obesity, SAT showed higher expression of genes related to adipocyte function, anti-inflammatory markers, extracellular matrix remodeling, lipid metabolism, cell-death regulation, oxidative stress protection, mRNA processing, and cholesterol handling compared to VAT. In contrast, VAT showed elevated expression of genes linked to inflammation, complement activation, stress signaling, cell death, lipid biosynthesis, and mRNA processing. Compared with controls, SAT in obesity showed increased inflammatory and stress-response gene expression and upregulation of RNA processing regulators, but reduced de novo lipogenesis and cholesterol synthesis. Following MBS, SAT showed restored expression of lipogenic and adipogenic genes alongside downregulation of inflammatory, cholesterol biosynthesis, and splicing-factor genes. Conclusions These findings demonstrate SAT and VAT remodeling in obesity and show that MBS partially reverses transcriptional changes in SAT, providing mechanistic insight into its metabolic benefits. They also highlight the need for targeted therapeutic strategies to more fully restore adipose tissue function and improve long-term metabolic outcomes. ClinicalTrials.gov registration numbers NCT00793143 and NCT01373892.