Impaired HDL function in obese adolescents: Impact of lifestyle intervention and bariatric surgery

Objective HDL regulates endothelial function via stimulation of nitric oxide production. It is documented that endothelial function is impaired in obese adolescents, and improved by lifestyle interventions (LI). Design and Methods HDL function in obese adolescents and the impact of LI or Roux-en-Y gastric bypass surgery (RYGB) was assessed. HDL was isolated from 14 adolescents with normal body mass index (HDL_control), 10 obese (HDL _obese) before and after 6 month LI, and five severe obese adolescents before and one year after RYGB. HDL-mediated phosphorylation of endothelial nitric oxide synthase (eNOS)-Ser¹¹⁷⁷, eNOS-Thr⁴⁹⁵, and PKC-ßII was evaluated. In addition the HDL proteome was analyzed. Results HDL_obese-mediated eNOS-Ser¹¹⁷⁷ phosphorylation was reduced, whereas eNOS-Thr⁴⁹⁵ phosphorylation increased significantly when compared to HDL_control. No impact of obesity was observed on PKC-ßII phosphorylation. LI and RYGB had no impact on HDL-mediated phosphorylation of eNOS and PKC-ßII. A principle component plot analysis of the HDL particle separated controls and severe obese, whereas the interventions did not trigger sufficient differences to the HDL proteome to permit distinction. Conclusion These results demonstrated that HDL-function is impaired in obese adolescents, and that LI or RYGB did not correct this dysfunction. This might be an argument for developing earlier prevention strategies in obese adolescents to avoid HDL dysfunction.