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

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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

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Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Chemistry(all)

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