Bariatric Surgery-induced High-density Lipoprotein Functionality Enhancement Is Associated With Reduced Inflammation

J Clin Endocrinol Metab. 2022 Jul 14;107(8):2182-2194. doi: 10.1210/clinem/dgac244.


Background: Emerging evidence suggests an association between impaired high-density lipoprotein (HDL) functionality and cardiovascular disease (CVD). HDL is essential for reverse cholesterol transport (RCT) and reduces inflammation and oxidative stress principally via paraoxonase-1 (PON1). RCT depends on HDL's capacity to accept cholesterol (cholesterol efflux capacity [CEC]) and active transport through ATP-binding cassette (ABC) A1, G1, and scavenger receptor-B1 (SR-B1). We have studied the impact of Roux-en-Y gastric bypass (RYGB) in morbidly obese subjects on RCT and HDL functionality.

Methods: Biomarkers associated with increased CVD risk including tumour necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hsCRP), myeloperoxidase mass (MPO), PON1 activity, and CEC in vitro were measured in 44 patients before and 6 and 12 months after RYGB. Overweight but otherwise healthy (mean body mass index [BMI] 28 kg/m2) subjects acted as controls. Twelve participants also underwent gluteal subcutaneous adipose tissue biopsies before and 6 months after RYGB for targeted gene expression (ABCA1, ABCG1, SR-B1, TNF-α) and histological analysis (adipocyte size, macrophage density, TNF-α immunostaining).

Results: Significant (P < 0.05) improvements in BMI, HDL-cholesterol, hsCRP, TNF-α, MPO mass, PON1 activity, and CEC in vitro were observed after RYGB. ABCG1 (fold-change, 2.24; P = 0.005) and ABCA1 gene expression increased significantly (fold-change, 1.34; P = 0.05). Gluteal fat adipocyte size (P < 0.0001), macrophage density (P = 0.0067), and TNF-α immunostaining (P = 0.0425) were reduced after RYBG and ABCG1 expression correlated inversely with TNF-α immunostaining (r = -0.71; P = 0.03).

Conclusion: RYGB enhances HDL functionality in association with a reduction in adipose tissue and systemic inflammation.

Keywords: ABCG1; HDL functionality; bariatric surgery; cardiovascular disease; cholesterol efflux capacity; inflammation; obesity.

MeSH terms

  • ATP Binding Cassette Transporter 1 / metabolism
  • Aryldialkylphosphatase
  • Bariatric Surgery*
  • C-Reactive Protein / metabolism
  • Cardiovascular Diseases*
  • Cholesterol / metabolism
  • Humans
  • Inflammation* / metabolism
  • Inflammation* / therapy
  • Lipoproteins, HDL* / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • ATP Binding Cassette Transporter 1
  • Lipoproteins, HDL
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein
  • Cholesterol
  • Aryldialkylphosphatase
  • PON1 protein, human