Women undergoing repeated bariatric surgery due to recurrent weight gain exhibit an inflammatory molecular and functional signature of subcutaneous adipose tissue
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Background
Repeated metabolic-bariatric surgery (MBS, r-BS) represents 10–25% of all MBS procedures and is commonly performed for recurrent weight gain after initial weight loss. How weight loss followed by regain reshapes adipose tissue biology remains unclear. We hypothesized that women undergoing r-BS exhibit a distinct adipose tissue signature compared with those undergoing primary bariatric surgery (p-BS).
Methods
We analyzed subcutaneous and visceral adipose tissues (SAT, VAT, respectively) from women undergoing either p-BS, or r-BS with documented, >15% weight-loss after prior MBS. Tissues were assessed histologically, molecularly, and functionally (activation of human microglia cells (HMC3) by SAT secretome).
Results
Consistent with other cohorts, women undergoing r-BS (n=21) trended to be older (47.2 vs. 40.5 y, p=0.06) than those undergoing p-BS (n=35), with a lower BMI (42.3 vs. 45.6 kg/m2, respectively, p=0.103), and a trend for improved cardiometabolic risk parameters such as fasting insulin, CRP and HDL-c. Adipose tissues’ histological features (adipocyte size, fibrosis, macrophage and crown-like structures abundance) were similar, while adipose mast-cells were slightly (though insignificantly) more prevalent in r-BS. Single-nucleus RNA-seq-based deconvolution algorithm applied unto bulk RNA-seq to uncover differences in cell composition confirmed the absence of a major shift in adipose tissue cell-type composition. Yet, it uncovered unique transcriptome of SAT, with activation of inflammatory pathways in r-BS. Consistently, SAT explants from r-BS secreted higher protein concentrations of NFκB-regulated cytokines IL6 and IL8. Biological impact of the more inflammatory secretome was demonstrated by its increased ability to inflammatory activate human microglia cells.
Conclusions
Prior BS with significant weight-loss-regain in women is associated with inflammatory transcriptome and secretome of SAT, possibly reflecting on adipose-brain endocrine communication.
