TY - JOUR
T1 - The association of human apolipoprotein C-III sialylation proteoforms with plasma triglycerides
AU - Yassine, Hussein N.
AU - Trenchevska, Olgica
AU - Ramrakhiani, Ambika
AU - Parekh, Aarushi
AU - Koska, Juraj
AU - Walker, Ryan W.
AU - Billheimer, Dean
AU - Reaven, Peter D.
AU - Yen, Frances T.
AU - Nelson, Randall W.
AU - Goran, Michael I.
AU - Nedelkov, Dobrin
N1 - Publisher Copyright:
© 2015, Public Library of Science. All rights reserved. This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
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U2 - 10.1371/journal.pone.0144138
DO - 10.1371/journal.pone.0144138
M3 - Article
C2 - 26633899
AN - SCOPUS:84956671120
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 12
M1 - e0144138
ER -