Inflammatory signature of subcutaneous fat after weight loss and regain in women undergoing repeated bariatric surgery

CONTEXT: Repeated metabolic-bariatric surgery (MBS, r-BS) represents 10-25% of all MBS and is commonly-performed for weight regain after prior significant weight-loss. It remains unclear how adipose tissue adapts to surgically-induced weight-loss-regain in obesity. OBJECTIVE: We hypothesized that compared to primary bariatric surgery (p-BS), women undergoing r-BS exhibit a distinct adipose tissue signature. DESIGN: Subcutaneous/visceral adipose tissues (SAT/VAT, respectively) from female MBS patients were assessed histologically/molecularly/functionally (activation of human microglia cells by SAT-secretome). SETTING: Elective MBS in a public university hospital. PATIENTS: Women undergoing either p-BS, or r-BS with documented >15% weight-loss after prior MBS. INTERVENTION: MBS. MAIN OUTCOME MEASUREMENT: Inflammation in SAT. RESULTS: Women undergoing r-BS (n=21) trended to be older than those undergoing p-BS (n=35)(47.2 vs. 40.5y, p=0.06), with a lower BMI (42.3 vs. 45.6 kg/m2, respectively, p=0.103), and a trend for improved cardiometabolic risk parameters (fasting insulin, CRP and HDL-c). Adipocyte size, adipose tissue fibrosis, macrophage and crown-like structures abundance were similar, while mast-cells were slightly more prevalent in r-BS. Single-nucleus RNA-seq-based deconvolution algorithm applied unto bulk RNA-seq confirmed the absence of a major shift in adipose tissue cell-type composition. Yet, RNA-seq revealed unique transcriptome of r-BS SAT, with activation of inflammatory pathways. Consistently, SAT explants from r-BS secreted higher protein concentrations of NFκB-regulated cytokines IL6/IL8. Functional impact of the more inflammatory-secretome was suggested by its increased ability to inflammatory-activate human microglia cells. CONCLUSIONS: Prior BS-induced weight-loss and subsequent regain in women is associated with inflammatory transcriptome and secretome of SAT that can activate cultured human microglia cells.