Novel insights into potential mechanisms by which bariatric surgery reduces cardiovascular disease risk: Oral communication

Background:Bariatric surgery (BS) reduces cardiovascular disease (CVD) in a weight-independent manner although the underlying mechanisms are not fully understood. Impaired high-density lipoprotein (HDL) function and systemic inflammation have been associated with CVD. HDL primarily protects against atherosclerosis by removing excess cholesterol from cells (reverse cholesterol transport [RCT]). RCT depends on HDL's capacity to accept cholesterol (cholesterol efflux capacity [CEC]) and active transport through the channels ATP-binding-cassette (ABC-) A1, G1 and scavenger receptor-B1 (SR-B1). Additionally, anti-inflammatory and anti-oxidative functions of HDL are mediated by paraoxonase-1. We studied the impact of BS on HDL function with a specific focus on RCT.Methods:37 patients undergoing bariatric surgery were prospectively assessed before surgery and then 12 months post-operatively. Markers of inflammation (Tumour Necrosis Factor- α [TNF-α]; C-reactive protein [CRP]), oxidative stress (myeloperoxidase mass and paraoxonase-1 activity) and CEC in vitro were measured in these patients. In addition, 12 participants had targeted gene expression (real-time quantitative PCR) of ABCA1, ABCG1, SRB1 and TNF-α in gluteal subcutaneous adipose tissue biopsy samples. To test for differences at the time-points, Wilcoxon matched-pair signed rank test was used.Results:Median HDL-C (1.18 to 1.4mmol/L;p<0.005), CEC (11.5 to 14.4%;p<0.005) and paraoxonase-1 activity (77 to 87nmol/ml/min;p<0.005) increased from baseline to 12 months post-surgically. Contrarily, median CRP (6.52 to 1.1mg/L;p<0.005), TNF-α (14.5pg/mL to undetectable;p<0.005) and myeloperoxidase mass (973 to 756ng/mL;p<0.005) reduced from baseline to 12 months post-operatively. Adipose tissue gene expression of ABCA1 (fold-change 1.34;p=0.05) and ABCG1 (fold-change, 2.24;p=0.005) were augmented whereas TNF-α (fold-change, 0.44;p=0.57) and SR-B1 (fold-change, 1.12;p=0.6) did not change significantly.Conclusions:Bariatric surgery results in an improvement in HDL function and reduction in both inflammation and oxidative stress. These findings potentially provide a novel insight into how the previously observed weight-independent reduction in CVD occurs after BS. This is the first study to comprehensively study RCT by analysing both HDL's CEC and the channels involved in active cholesterol transport. The findings of this study may allow for other interventions that improve RCT in a multi-faceted approach as previous drug interventional trials have predominantly focused only on increasing HDL-C cargo (and therefore possibly CEC) without considering active transport channels.

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