Site-Specific Glycoprofiles of HDL-Associated ApoE are Correlated with HDL Functional Capacity and Unaffected by Short-Term Diet

Chenghao Zhu, Maurice Wong, Qiongyu Li, Lisa Sawrey-Kubicek, Elizabeth Beals, Chris H. Rhodes, Romina Sacchi, Carlito B. Lebrilla, Angela M. Zivkovic

Research output: Contribution to journalArticle

Abstract

Since high-density lipoprotein (HDL) glycoprofiles are associated with HDL functional capacity, we set out to determine whether diet can alter the glycoprofiles of key HDL-associated proteins, including ApoE, a potent driver of chronic disease risk. Ten healthy subjects consumed a fast food (FF) and a Mediterranean (Med) diet for 4 days in randomized order, with a 4-day wash-out between treatments. A multiple reaction monitoring method was used to characterize the site-specific glycoprofiles of HDL proteins, and HDL functional capacity was analyzed. We describe for the first time that ApoE has 7 mucin-type O-glycosylation sites, which were not affected by short-term diet. The glycoprofiles of other HDL-associated proteins were also unaffected, except that a disialylated ApoC-III glycan was enriched after Med diet, and a nonsialylated ApoC-III glycan was enriched after FF diet. Twenty-five individual glycopeptides were significantly correlated with cholesterol efflux capacity and 21 glycopeptides were correlated with immunomodulatory capacity. Results from this study indicate that the glycoprofiles of HDL-associated proteins including ApoE are correlated with HDL functional capacity but generally unaffected by diet in the short term, except ApoC-III sialylation. These results suggest that HDL protein glycoprofiles are affected by both acute and long-term factors and may be useful for biomarker discovery.

Original languageEnglish (US)
JournalJournal of Proteome Research
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Apolipoproteins E
HDL Lipoproteins
Nutrition
Diet
Apolipoprotein C-III
Mediterranean Diet
Fast Foods
Glycopeptides
Proteins
Polysaccharides
Glycosylation
Biomarkers
Mucins
Healthy Volunteers
Chronic Disease
Cholesterol
Monitoring

Keywords

  • ApoC-III
  • ApoE
  • cholesterol efflux
  • fast food diet
  • glycomics
  • glycoproteomics
  • high-density lipoprotein
  • Mediterranean diet

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

Cite this

Site-Specific Glycoprofiles of HDL-Associated ApoE are Correlated with HDL Functional Capacity and Unaffected by Short-Term Diet. / Zhu, Chenghao; Wong, Maurice; Li, Qiongyu; Sawrey-Kubicek, Lisa; Beals, Elizabeth; Rhodes, Chris H.; Sacchi, Romina; Lebrilla, Carlito B.; Zivkovic, Angela M.

In: Journal of Proteome Research, 01.01.2019.

Research output: Contribution to journalArticle

Zhu, Chenghao ; Wong, Maurice ; Li, Qiongyu ; Sawrey-Kubicek, Lisa ; Beals, Elizabeth ; Rhodes, Chris H. ; Sacchi, Romina ; Lebrilla, Carlito B. ; Zivkovic, Angela M. / Site-Specific Glycoprofiles of HDL-Associated ApoE are Correlated with HDL Functional Capacity and Unaffected by Short-Term Diet. In: Journal of Proteome Research. 2019.
@article{604de418fb894c549adcf79b4423132f,
title = "Site-Specific Glycoprofiles of HDL-Associated ApoE are Correlated with HDL Functional Capacity and Unaffected by Short-Term Diet",
abstract = "Since high-density lipoprotein (HDL) glycoprofiles are associated with HDL functional capacity, we set out to determine whether diet can alter the glycoprofiles of key HDL-associated proteins, including ApoE, a potent driver of chronic disease risk. Ten healthy subjects consumed a fast food (FF) and a Mediterranean (Med) diet for 4 days in randomized order, with a 4-day wash-out between treatments. A multiple reaction monitoring method was used to characterize the site-specific glycoprofiles of HDL proteins, and HDL functional capacity was analyzed. We describe for the first time that ApoE has 7 mucin-type O-glycosylation sites, which were not affected by short-term diet. The glycoprofiles of other HDL-associated proteins were also unaffected, except that a disialylated ApoC-III glycan was enriched after Med diet, and a nonsialylated ApoC-III glycan was enriched after FF diet. Twenty-five individual glycopeptides were significantly correlated with cholesterol efflux capacity and 21 glycopeptides were correlated with immunomodulatory capacity. Results from this study indicate that the glycoprofiles of HDL-associated proteins including ApoE are correlated with HDL functional capacity but generally unaffected by diet in the short term, except ApoC-III sialylation. These results suggest that HDL protein glycoprofiles are affected by both acute and long-term factors and may be useful for biomarker discovery.",
keywords = "ApoC-III, ApoE, cholesterol efflux, fast food diet, glycomics, glycoproteomics, high-density lipoprotein, Mediterranean diet",
author = "Chenghao Zhu and Maurice Wong and Qiongyu Li and Lisa Sawrey-Kubicek and Elizabeth Beals and Rhodes, {Chris H.} and Romina Sacchi and Lebrilla, {Carlito B.} and Zivkovic, {Angela M.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1021/acs.jproteome.9b00450",
language = "English (US)",
journal = "Journal of Proteome Research",
issn = "1535-3893",
publisher = "American Chemical Society",

}

TY - JOUR

T1 - Site-Specific Glycoprofiles of HDL-Associated ApoE are Correlated with HDL Functional Capacity and Unaffected by Short-Term Diet

AU - Zhu, Chenghao

AU - Wong, Maurice

AU - Li, Qiongyu

AU - Sawrey-Kubicek, Lisa

AU - Beals, Elizabeth

AU - Rhodes, Chris H.

AU - Sacchi, Romina

AU - Lebrilla, Carlito B.

AU - Zivkovic, Angela M.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Since high-density lipoprotein (HDL) glycoprofiles are associated with HDL functional capacity, we set out to determine whether diet can alter the glycoprofiles of key HDL-associated proteins, including ApoE, a potent driver of chronic disease risk. Ten healthy subjects consumed a fast food (FF) and a Mediterranean (Med) diet for 4 days in randomized order, with a 4-day wash-out between treatments. A multiple reaction monitoring method was used to characterize the site-specific glycoprofiles of HDL proteins, and HDL functional capacity was analyzed. We describe for the first time that ApoE has 7 mucin-type O-glycosylation sites, which were not affected by short-term diet. The glycoprofiles of other HDL-associated proteins were also unaffected, except that a disialylated ApoC-III glycan was enriched after Med diet, and a nonsialylated ApoC-III glycan was enriched after FF diet. Twenty-five individual glycopeptides were significantly correlated with cholesterol efflux capacity and 21 glycopeptides were correlated with immunomodulatory capacity. Results from this study indicate that the glycoprofiles of HDL-associated proteins including ApoE are correlated with HDL functional capacity but generally unaffected by diet in the short term, except ApoC-III sialylation. These results suggest that HDL protein glycoprofiles are affected by both acute and long-term factors and may be useful for biomarker discovery.

AB - Since high-density lipoprotein (HDL) glycoprofiles are associated with HDL functional capacity, we set out to determine whether diet can alter the glycoprofiles of key HDL-associated proteins, including ApoE, a potent driver of chronic disease risk. Ten healthy subjects consumed a fast food (FF) and a Mediterranean (Med) diet for 4 days in randomized order, with a 4-day wash-out between treatments. A multiple reaction monitoring method was used to characterize the site-specific glycoprofiles of HDL proteins, and HDL functional capacity was analyzed. We describe for the first time that ApoE has 7 mucin-type O-glycosylation sites, which were not affected by short-term diet. The glycoprofiles of other HDL-associated proteins were also unaffected, except that a disialylated ApoC-III glycan was enriched after Med diet, and a nonsialylated ApoC-III glycan was enriched after FF diet. Twenty-five individual glycopeptides were significantly correlated with cholesterol efflux capacity and 21 glycopeptides were correlated with immunomodulatory capacity. Results from this study indicate that the glycoprofiles of HDL-associated proteins including ApoE are correlated with HDL functional capacity but generally unaffected by diet in the short term, except ApoC-III sialylation. These results suggest that HDL protein glycoprofiles are affected by both acute and long-term factors and may be useful for biomarker discovery.

KW - ApoC-III

KW - ApoE

KW - cholesterol efflux

KW - fast food diet

KW - glycomics

KW - glycoproteomics

KW - high-density lipoprotein

KW - Mediterranean diet

UR - http://www.scopus.com/inward/record.url?scp=85073007081&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85073007081&partnerID=8YFLogxK

U2 - 10.1021/acs.jproteome.9b00450

DO - 10.1021/acs.jproteome.9b00450

M3 - Article

C2 - 31545048

AN - SCOPUS:85073007081

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

ER -