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• W3136499399 abstract "Metabolicsyndrome (MetS) increases the risk of type 2-diabetes (T2D) and cardiovasculardisease (CVD) due in part to altered lipid metabolism and homeostasis. Suchmetabolic diseases are commonly associated with lower high-densitylipoprotein-cholesterol (HDL-C) and decreased functionality, which areconsidered as independent risk factors for CVD. The lipid composition of HDLmay contribute to the HDL functional deficiency in metabolic disease patients.    Weight loss and exercise are recommended as a first-linetreatment to delay the onset or prevent the progression of T2D and CVD and theirassociated complications. This may represent a promising approach to normaliselipid metabolism and thereby HDL lipid composition and ultimately enhance HDLfunction. In this study, we have used a lipidomic approach to characterise thedifferences in the plasma and HDL lipidomes between MetS patients and healthyindividuals. We have combined this with HDL particle size, cholesterol effluxcapacity (CEC) and cholesteryl ester transfer protein (CETP) measurements todefine the relationships between the HDL lipidome, particle size and CEC. Wehave also assessed the effect of dietary weight loss (WL) and dietary weightloss plus exercise (WLEX) treatments on the structure composition and functionof HDL particles.    MetS patients (N=95) were recruited; subsets underwent12-weeks of no treatment (n=17), WL (n=19), or (WLEX (n=17). A set of plasmasamples from age and sex matched healthy individuals were also included. HDLwas isolated using density-gradient ultracentrifugation. The plasma and HDLlipidomes (333 species) were analysed by mass spectrometry and the HDL particlesize profile was determined by nuclear magnetic resonance. Cholesteryl estertransfer protein (CETP) activity and ex vivo HDL-cholesterol efflux capacity(CEC) were assessed.    Compared to the healthy individuals, the MetS patients showedsimilar plasma and HDL lipid abnormalities to those that have been observedpreviously in T2D and CVD, particularly in sphingolipids, ether-phospholipids,and di- and triacylglycerol. In MetS patients, the HDL particle profile wasshifted toward a smaller particle size, and CEC was lower compared with thehealthy individuals. Several HDL lipid classes and species were associated withHDL diameter and CEC. Importantly, we observed normalisation effects toward thehealthy individuals in plasma and HDL lipid species, including dihydroceramide,ceramide, lysoalkylphosphatidylcholine, cholesterol ester and di- andtriacylglycerols, following WL and WLEX, with greater effects being observed inthe WLEX group. Similarly, HDL particle profile showed increased particle sizeafter the WL and WLEX treatments, with greater effects being observed in thelatter group. CETP activity was also reduced after the WL and WLEXinterventions, and CEC was improved significantly only after WLEX.    The plasma and HDL lipidomes are significantly altered inMetS, leading to a higher risk of insulin resistance, T2D and CVD. Dietarymodifications and exercise treatment in MetS patients attenuate severalimportant abnormalities in the plasma and HDL lipidomes and HDL particle sizeprofile and ultimately enhance HDL function. HDL lipids associated with reducedparticle size and diminished CEC may represent novel biomarkers for the earlyprediction of HDL dysfunction and potential therapeutic targets for future HDLmodifying therapies." @default.
• W3136499399 created "2021-03-29" @default.
• W3136499399 creator A5040313874 @default.
• W3136499399 date "2017-02-13" @default.
• W3136499399 modified "2023-09-24" @default.
• W3136499399 title "Analysis of the Plasma and HDL Lipidomes in Metabolic Syndrome Patients Following Weight Loss and Weight Loss Plus Exercise Treatments" @default.
• W3136499399 doi "https://doi.org/10.4225/03/58a14051dd5d1" @default.
• W3136499399 hasPublicationYear "2017" @default.
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