Background: Emerging evidence suggests that impaired high density lipoprotein (HDL) function is associated with cardiovascular disease (CVD). HDL is essential for removing excess circulating cholesterol by reverse cholesterol transport (RCT). Additionally HDL reduces inflammation and oxidative stress, especially through paraoxonase-1. Whereas HDLs capacity to accept cholesterol from peripheral cells is key (i.e. cholesterol efflux capacity (CEC)), successful RCT depends on the transporters ATP-binding-cassette (ABC-) A1, G1 and scavenger receptor-B1 (SR-B1). Previous studies suggest weight-independent reductions in CVD after bariatric surgery (BS) although the exact mechanisms are unclear. We studied the impact of BS on HDL function with a specific focus on the principal components of RCT (CEC and transporters).
Methods: 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 from 37 patients before, 6 and 12 months after BS. 12 participants had targeted gene expression (real-time quantitative PCR) of ABCA1, ABCG1, SR-B1 and TNF-α in gluteal subcutaneous adipose tissue biopsy samples. Results shown represent medians (interquartile range).
Results: HDL-C levels increased significantly 12 months after BS (1.18 mmol/l (1.001.33) at baseline to 1.4 mmol/l (1.21.7); P<0.0001). CRP, CETP and myeloperoxidase mass decreased with enhancements in CEC (Table). Serum TNF-α levels reduced from 14.5 pg/ml (1.558) to 2.3 pg/ml (051.8) to being undetectable (03 pg/ml) at 6 and 12 months post-surgery respectively (P<0.0001). Changes in HDL-C correlated significantly with changes in CRP (r=−0.37; P<0.05) and paraoxonase-1 (r=0.43; P<0.05). 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 expression decreased non-significantly (fold-change 0.44; P=0.57). SR-B1 expression did not change (fold-change 1.12; P=0.6).
Conclusion: HDL function improves post-operatively with augmentation of RCT potentially contributing to reduction in CVD after BS.
|Test||Median Baseline||Median 6 months||Median 12 months|
|CEC (%)||11.5 (10.514.6)||12.9 (9.715.2)||14.4 ¥* (1318.4)|
|Myeloperoxidase mass (ng/ml)||973.1 (519.91460.8)||988.4 (515.81389.4)||756.0 ¥* (211.51162.6)|
|Cholesterol-Ester Transfer Protein Activity (nmol/ml/hr)||31.4 (13.6)||24.6 T (12.9)||27.0¥ (11.7)|
|Paraoxonase-1 Activity (nmol/ml/min)||77 (57175)||83 (57169)||87* (59211)|
|CRP (mg/l)||6.52 (4.511.1)||3.2T (1.35.3)||1.1¥* (0.53.0)|
|Symbols denote P<0.005: ¥12 v baseline; *12 v 6; T6 v baseline|