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.
We aimed to determine the risk factors associated with the depletion of large HDL particles and enrichment of small HDL particles observed in adolescents with T2D. Four groups of adolescents were recruited: ) lean insulin-sensitive (L-IS), normal BMI and no insulin resistance;) lean insulin-resistant (L-IR), normal BMI but insulin resistance (fasting insulin levels ≥ 25 mU/ml and homeostatic model assessment of insulin resistance ≥ 6); ) obese insulin-sensitive (O-IS), BMI ≥ 95th percentile and no insulin resistance; and) obese insulin-resistant (O-IR), BMI ≥ 95th percentile and insulin resistance. Plasma was separated by using gel-filtration chromatography to assess the HDL subspecies profile and compared with that of obese adolescents with T2D (O-T2D). Large HDL subspecies were significantly lower across groups from L-IS > L-IR > O-IS > O-IR > O-T2D ( < 0.0001); small HDL particles were higher from L-IS to O-T2D ( < 0.0001); and medium-sized particles did not differ across groups. The contributions of obesity, insulin resistance, and diabetes to HDL subspecies profile were between 23% and 28%, 1% and 10%, and 4% and 9%, respectively. Obesity is the major risk factor associated with the altered HDL subspecies profile previously reported in adolescents with T2D, with smaller contributions from insulin resistance and diabetes.
Severe obesity is a major problem among US adolescents and traditional weight loss strategies, including lifestyle intervention, have had limited efficacy. Bariatric surgery has grown in popularity because it results in rapid weight loss while improving cardiovascular disease risk factors, including raising high density lipoprotein cholesterol (HDL-C). Whether this rise in HDL-C translates into improved HDL cardioprotective function is not clear, particularly in adolescents. We studied the impact of weight loss surgery (vertical sleeve gastrectomy) in adolescents with severe obesity on HDL function pre and one year post operatively. Adolescents underwent laparoscopic vertical sleeve gastrectomy between in 2008-2011. HDL function (cholesterol efflux, HDL oxidation, and HDL inflammatory index) was measured pre and post-surgery on stored serum (-80°C) after apolipoprotein B depletion with polyethylene glycol. Only males were studied in this pilot study to minimize the known effects of sex and the menstrual cycle on lipoproteins. Changes pre and post-surgery were evaluated using paired t-tests. Participants (n=10, 90% Caucasian) were a mean±SD age of 17.4±1.6 years at baseline and 18.4 ±1.5 years at follow-up. After vertical sleeve gastrectomy, BMI was 32% lower than baseline (p<0.01). All lipid measurements improved and HDL-C increased by 23%. HDL function significantly improved post vertical sleeve gastrectomy compared to baseline, all p<0.01 (cholesterol efflux by 12%, HDL oxidation potential by 30%, and HDL inflammatory index by 25%). We conclude that vertical sleeve gastrectomy results in a significant improvement in HDL cholesterol levels and HDL function in adolescents with severe obesity. Whether these changes result in long term improvement in cardiovascular health remains to be determined.
We have shown that adolescents with type 2 diabetes have an altered HDL subspecies profile, characterized by a depletion of large apoE rich HDL particles. We have also shown a significant inverse relationship between this profile and arterial stiffness suggesting that the loss of these particles is associated with early atherosclerosis. We sought to evaluate known risk factors (that contribute to the depletion of large HDL subspecies in adolescents. We evaluated the contributions of obesity, insulin resistance and diabetes to loss of large HDL particles, in five adolescent groups (n=20 per group) with highly specific phenotypes. Insulin resistance was defined by fasting insulin levels and HOMA-IR Adolescent groups were: lean insulin sensitive (normal body mass index (BMI) with no insulin resistance; lean insulin resistant (normal BMI with insulin resistance), obese insulin sensitive (obese BMI with no insulin resistance), obese insulin resistant (obese BMI with insulin resistance), and with type 2 diabetes (obese with insulin resistance and type 2 diabetes by the American Diabetes Association criteria). Stored plasma from each participant was fractionated using gel filtration chromatography to isolate HDL subspecies. The mean age of the cohort was 17.9 ± 1.6 years. Groups did not differ in age and race (50% Caucasian, 50% African American, all male). Large rich HDL subspecies declined significantly across each group from lean insulin sensitive, to lean insulin resistant, to obese insulin sensitive, to obese insulin resistant to type 2 diabetes (p<0.0001). An inverse relationship was also seen for small HDL particles (p<0.0001). Medium size particles did not differ across groups. These data were confirmed by nuclear magnetic resonance spectroscopy. Obesity explained ~50%, insulin resistance ~ 25%, and diabetes ~10% of the decline in large particles between lean insulin sensitive to type 2 diabetes participants. Twenty percent remained unexplained. Obesity appears to drive the decline in large atheroprotective HDL particles in male adolescents. However, contributions of insulin resistance and type 2 diabetes are evident. Whether weight loss reverses this profile and has the potential to improve cardiovascular risk remains to be determined.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.