Weight loss surgery in adolescents corrects high-density lipoprotein subspecies and their function

Abstract

Background/ObjectiveYouth with obesity have an altered HDL subspecies profile characterized by depletion of large apoE rich HDL particles and an enrichment of small HDL particles. The goal of this study was to test the hypothesis that this atherogenic HDL profile would be reversed and that HDL function would improve with metabolic surgery.MethodsSerum samples from adolescent males with severe obesity mean ± SD age of 17.4 ± 1.6 years were studied at baseline and 1 year following vertical sleeve gastrectomy (VSG). HDL subspecies and HDL function were evaluated pre and post VSG using paired t-tests. A lean group of adolescents was included as a reference group.ResultsAfter VSG, BMI decreased by 32% and insulin resistance as estimated by HOMA-IR decreased by 75% (both p<0.01). Large apoE rich HDL subspecies increased following VSG (p<0.01) and approached that of lean adolescents despite participants with considerable residual obesity. Additionally, HDL function improved compared to baseline (cholesterol efflux capacity increased by 12%, HDL lipid peroxidation potential decreased by 30%, and HDL anti-oxidative capacity improved by 25%, all p<0.01).ConclusionsMetabolic surgery results in a significant improvement in the quantity of large HDL subspecies and HDL function. Our data suggest metabolic surgery may improve cardiovascular risk in adolescents and young adults.

Cell-free Biochemical Fluorometric Enzymatic Assay for High-throughput Measurement of Lipid Peroxidation in High Density Lipoprotein

“…In our prior published studies with cryopreserved HDL, this method was able to demonstrate at least 10% relative differences in HDLox compared to HDL from control groups (without disease e.g. chronic HIV infection) 36,37,38 .…”

“…We have used the fluorochrome HDL function assay to detect impaired HDL function in states of chronic oxidative stress such as atherosclerosis and Human Immunodeficiency Virus infection (HIV) 32 . Using biochemical assay of HDL function, several studies have confirmed the association of HDLox with obesity and cardiovascular disease 19,21,27,34,35,36,47 . Significantly, in human pilot studies we demonstrated associations of HDLox with validated cell-based assays, surrogate measures of cardiovascular disease, systemic inflammation, immune dysfunction and associated cardiovascular and metabolic risk phenotypes 32,36 .…”

“…Using biochemical assay of HDL function, several studies have confirmed the association of HDLox with obesity and cardiovascular disease 19,21,27,34,35,36,47 . Significantly, in human pilot studies we demonstrated associations of HDLox with validated cell-based assays, surrogate measures of cardiovascular disease, systemic inflammation, immune dysfunction and associated cardiovascular and metabolic risk phenotypes 32,36 . Although this assay has been used in several studies to address the role of HDL function in different diseases such as chronic HIV infection 32,38 , atherosclerosis 32 and obesity 36 , it remains to be validated in large scale studies with available clinical endpoints of CVD (e.g.…”

“…Higher HDLox values are associated with reduced HDL antioxidant function. The readout of this assay is associated with validated cell-based assays, surrogate measures of cardiovascular disease, systemic inflammation, immune dysfunction and associated cardiovascular and metabolic risk phenotypes 19,21,27,32,34,35,36,37,38,39,47 . This method offers a convenient, yet robust tool for examining the role of HDL function in human disease.…”

“…We have shown that this fluorescence-based approach does not have the limitations of prior HDL function assays 27,28 . This assay has been further refined and standardized in our laboratory so that it can reliably be used in large scale human studies even with cryopreserved plasma 32,33,34,35,36,37,38,39,40,41,42 . The readout of this assay is associated with readouts of validated cell-based assays, surrogate measures of cardiovascular disease, systemic inflammation, immune dysfunction and associated cardiovascular and metabolic risk phenotypes 32,33,34,35,36,37,38,39 .…”