The association of human apolipoprotein C-III sialylation proteoforms with plasma triglycerides

Hussein N. Yassine, Olgica Trenchevska, Ambika Ramrakhiani, Aarushi Parekh, Juraj Koska, Ryan W. Walker, Dean Billheimer, Peter D. Reaven, Frances T. Yen, Randall W. Nelson, Michael I. Goran, Dobrin Nedelkov

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17 Scopus citations

Abstract

Introduction: Apolipoprotein C-III (apoC-III) regulates triglyceride (TG) metabolism. In plasma, apoC-III exists in non-sialylated (apoC-III0a without glycosylation and apoC-III0b with glycosylation), monosialylated (apoC-III1) or disialylated (apoC-III2) proteoforms. Our aim was to clarify the relationship between apoC-III sialylation proteoforms with fasting plasma TG concentrations. Methods: In 204 non-diabetic adolescent participants, the relative abundance of apoC-III plasma proteoforms was measured using mass spectrometric immunoassay. Results: Compared with the healthy weight subgroup (n = 16), the ratios of apoC-III0a, apoC-III0b, and apoC-III1 to apoC-III2 were significantly greater in overweight (n = 33) and obese participants (n = 155). These ratios were positively correlated with BMI z-scores and negatively correlated with measures of insulin sensitivity (Si). The relationship of apoC-III1/apoC-III2 with Si persisted after adjusting for BMI (p = 0.02). Fasting TG was correlated with the ratio of apoC-III0a/apoC-III2 (r = 0.47, p<0.001), apoC-III0b/apoC-III2 (r = 0.41, p<0.001), apoC-III1/apoC-III2 (r = 0.43, p<0.001). By examining apoC-III concentrations, the association of apoC-III proteoforms with TG was driven by apoC-III0a (r = 0.57, p<0.001), apoC-III0b (r = 0.56. p<0.001) and apoC-III1 (r = 0.67, p<0.001), but not apoC-III2 (r = 0.006, p = 0.9) concentrations, indicating that apoC-III relationship with plasma TG differed in apoC-III2 compared with the other proteoforms. Conclusion: We conclude that apoC-III0a, apoC-III0b, and apoC-III1, but not apoC-III2 appear to be under metabolic control and associate with fasting plasma TG. Measurement of apoC-III proteoforms can offer insights into the biology of TG metabolism in obesity.

Original languageEnglish (US)
Article numbere0144138
JournalPloS one
Volume10
Issue number12
DOIs
StatePublished - Dec 1 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Yassine, H. N., Trenchevska, O., Ramrakhiani, A., Parekh, A., Koska, J., Walker, R. W., Billheimer, D., Reaven, P. D., Yen, F. T., Nelson, R. W., Goran, M. I., & Nedelkov, D. (2015). The association of human apolipoprotein C-III sialylation proteoforms with plasma triglycerides. PloS one, 10(12), [e0144138]. https://doi.org/10.1371/journal.pone.0144138