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

Arterioscler Thromb Vasc Biol

Anmar A. Khan, Piyushkumar A. Mundra, Nora E. Straznicky, Paul J. Nestel, Gerard Wong, Ricardo Tan, Kevin Huynh, Theodore W. Ng, Natalie A. Mellett, Jacquelyn M. Weir, Christopher K. Barlow, Zahir H. Alshehry, Gavin W. Lambert, Bronwyn A. Kingwell, Peter J. Meikle

Research output: Contribution to journalArticleResearchpeer-review

6 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)438-447
Number of pages10
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume38
Issue number2
DOIs
Publication statusPublished - 1 Feb 2018

Keywords

  • cardiovascular diseases
  • cholesterol ester transfer proteins
  • cholesterol, HDL
  • metabolic syndrome
  • weight loss

Cite this

Khan, Anmar A. ; Mundra, Piyushkumar A. ; Straznicky, Nora E. ; Nestel, Paul J. ; Wong, Gerard ; Tan, Ricardo ; Huynh, Kevin ; Ng, Theodore W. ; Mellett, Natalie A. ; Weir, Jacquelyn M. ; Barlow, Christopher K. ; Alshehry, Zahir H. ; Lambert, Gavin W. ; Kingwell, Bronwyn A. ; Meikle, Peter J. / Weight Loss and Exercise Alter the High-Density Lipoprotein Lipidome and Improve High-Density Lipoprotein Functionality in Metabolic Syndrome : Arterioscler Thromb Vasc Biol. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2018 ; Vol. 38, No. 2. pp. 438-447.
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title = "Weight Loss and Exercise Alter the High-Density Lipoprotein Lipidome and Improve High-Density Lipoprotein Functionality in Metabolic Syndrome: Arterioscler Thromb Vasc Biol",
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.",
keywords = "cardiovascular diseases, cholesterol ester transfer proteins, cholesterol, HDL, metabolic syndrome, weight loss",
author = "Khan, {Anmar A.} and Mundra, {Piyushkumar A.} and Straznicky, {Nora E.} and Nestel, {Paul J.} and Gerard Wong and Ricardo Tan and Kevin Huynh and Ng, {Theodore W.} and Mellett, {Natalie A.} and Weir, {Jacquelyn M.} and Barlow, {Christopher K.} and Alshehry, {Zahir H.} and Lambert, {Gavin W.} and Kingwell, {Bronwyn A.} and Meikle, {Peter J.}",
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Weight Loss and Exercise Alter the High-Density Lipoprotein Lipidome and Improve High-Density Lipoprotein Functionality in Metabolic Syndrome : Arterioscler Thromb Vasc Biol. / Khan, Anmar A.; Mundra, Piyushkumar A.; Straznicky, Nora E.; Nestel, Paul J.; Wong, Gerard; Tan, Ricardo; Huynh, Kevin; Ng, Theodore W.; Mellett, Natalie A.; Weir, Jacquelyn M.; Barlow, Christopher K.; Alshehry, Zahir H.; Lambert, Gavin W.; Kingwell, Bronwyn A.; Meikle, Peter J.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 38, No. 2, 01.02.2018, p. 438-447.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Weight Loss and Exercise Alter the High-Density Lipoprotein Lipidome and Improve High-Density Lipoprotein Functionality in Metabolic Syndrome

T2 - Arterioscler Thromb Vasc Biol

AU - Khan, Anmar A.

AU - Mundra, Piyushkumar A.

AU - Straznicky, Nora E.

AU - Nestel, Paul J.

AU - Wong, Gerard

AU - Tan, Ricardo

AU - Huynh, Kevin

AU - Ng, Theodore W.

AU - Mellett, Natalie A.

AU - Weir, Jacquelyn M.

AU - Barlow, Christopher K.

AU - Alshehry, Zahir H.

AU - Lambert, Gavin W.

AU - Kingwell, Bronwyn A.

AU - Meikle, Peter J.

PY - 2018/2/1

Y1 - 2018/2/1

N2 - 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.

AB - 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.

KW - cardiovascular diseases

KW - cholesterol ester transfer proteins

KW - cholesterol, HDL

KW - metabolic syndrome

KW - weight loss

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U2 - 10.1161/ATVBAHA.117.310212

DO - 10.1161/ATVBAHA.117.310212

M3 - Article

VL - 38

SP - 438

EP - 447

JO - Arteriosclerosis, Thrombosis and Vascular Biology

JF - Arteriosclerosis, Thrombosis and Vascular Biology

SN - 1079-5642

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ER -