Weight loss plus exercise normalizes the HDL lipidome, lowers CETP activity, and boosts cholesterol efflux capacity in metabolic syndrome (Arterioscler Thromb Vasc Biol 2018)

Original title: Weight Loss and Exercise Alter the High-Density Lipoprotein Lipidome and Improve High-Density Lipoprotein Functionality in Metabolic Syndrome

Arterioscler Thromb Vasc Biol · 28 December 2017 · 7

Khan AA, Mundra PA, Straznicky NE, Nestel PJ, Wong G, Tan R, Huynh K, Ng TW, Mellett NA, Weir JM, Barlow CK, Alshehry ZH et al.

Comparing 95 patients with metabolic syndrome and 40 healthy individuals, the HDL lipidome in metabolic syndrome patients was substantially altered, with smaller mean particle size and lower cholesterol efflux capacity than in healthy individuals. Subsets of the metabolic syndrome group underwent 12 weeks of no treatment (n = 17), weight loss (n = 19), or weight loss plus exercise (WLEX, n = 17). Cholesteryl ester transfer protein (CETP) activity was reduced after both weight loss and WLEX, and cholesterol efflux capacity improved after WLEX, with the HDL lipidome and particle size shifting toward the healthy profile, and greater effects seen with WLEX. Several HDL phospholipid and sphingolipid species were associated with HDL diameter and cholesterol efflux capacity, suggesting these HDL lipids could serve as biomarkers of HDL dysfunction.

Original abstract

Objective: High-density lipoprotein (HDL) lipid composition and function may better reflect cardiovascular risk than HDL cholesterol concentration. This study characterized the relationships between HDL composition, metabolism, and function in metabolic syndrome (MetS) patients and how changes in composition after weight loss (WL) and exercise treatments are related to function.

Approach And Results: Plasma samples from MetS patients (n=95) and healthy individuals (n=40) were used in this study. Subsets of the MetS group underwent 12 weeks of no treatment (n=17), WL (n=19), or WL plus exercise (WLEX; n=17). HDL was isolated using density-gradient ultracentrifugation. The HDL lipidome was analyzed by mass spectrometry, and particle size determined by nuclear magnetic resonance. Cholesteryl ester transfer protein activity and ex vivo HDL cholesterol efflux capacity (CEC) were assessed. The HDL lipidome in the MetS patients was substantially different from that in healthy individuals, mean particle size was smaller, and CEC was lower. Several HDL phospholipid and sphingolipid species were associated with HDL diameter and CEC. The HDL lipidome and particle size were modified toward the healthy individuals after WL and WLEX treatments, with greater effects observed in the latter group. Cholesteryl ester transfer protein activity was reduced after WL and WLEX, and CEC was improved after WLEX.

Conclusions: WLEX treatment in MetS patients normalizes the HDL lipidome and particle size profile and enhances CEC. HDL lipids associated with diminished CEC may represent novel biomarkers for early prediction of HDL dysfunction and disease risk and may represent potential therapeutic targets for future HDL therapies.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00163943.

Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.