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

J Proteome Res. 2019 Nov 1;18(11):3977-3984. doi: 10.1021/acs.jproteome.9b00450. Epub 2019 Oct 1.


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; Mediterranean diet; cholesterol efflux; fast food diet; glycomics; glycoproteomics; high-density lipoprotein.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Apolipoprotein C-III / metabolism
  • Apolipoproteins E / metabolism*
  • Binding Sites
  • Cross-Over Studies
  • Diet*
  • Diet, Mediterranean
  • Fast Foods
  • Female
  • Glycoproteins / metabolism*
  • Glycosylation
  • Humans
  • Lipoproteins, HDL / metabolism*
  • Male
  • Proteome / metabolism*
  • Proteomics / methods*
  • Young Adult


  • Apolipoprotein C-III
  • Apolipoproteins E
  • Glycoproteins
  • Lipoproteins, HDL
  • Proteome