Yassine Hussein N, Trenchevska Olgica, Ramrakhiani Ambika, Parekh Aarushi, Koska Juraj, Walker Ryan W, Billheimer Dean, Reaven Peter D, Yen Frances T, Nelson Randall W, Goran Michael I, Nedelkov Dobrin
Department of Medicine, University of Southern California, Los Angeles, United States of America.
The Biodesign Institute, Arizona State University, Tempe, AZ, United States of America.
PLoS One. 2015 Dec 3;10(12):e0144138. doi: 10.1371/journal.pone.0144138. eCollection 2015.
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.
In 204 non-diabetic adolescent participants, the relative abundance of apoC-III plasma proteoforms was measured using mass spectrometric immunoassay.
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.
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.
载脂蛋白C-III（apoC-III）调节甘油三酯（TG）代谢。在血浆中，apoC-III以非唾液酸化形式（无糖基化的apoC-III0a和有糖基化的apoC-III0b）、单唾液酸化形式（apoC-III1）或双唾液酸化形式（apoC-III2）的蛋白亚型存在。我们的目的是阐明apoC-III唾液酸化蛋白亚型与空腹血浆TG浓度之间的关系。
在204名非糖尿病青少年参与者中，使用质谱免疫分析法测量apoC-III血浆蛋白亚型的相对丰度。
与健康体重亚组（n = 16）相比，超重（n = 33）和肥胖参与者（n = 155）中apoC-III0a、apoC-III0b和apoC-III1与apoC-III2的比率显著更高。这些比率与BMI z评分呈正相关，与胰岛素敏感性（Si）指标呈负相关。在调整BMI后，apoC-III1 / apoC-III2与Si的关系仍然存在（p = 0.02）。空腹TG与apoC-III0a / apoC-III2的比率相关（r = 0.47，p<0.001），apoC-III0b / apoC-III2的比率相关（r = 0.41，p<0.001），apoC-III1 / apoC-III2的比率相关（r = 0.43，p<0.001）。通过检查apoC-III浓度，apoC-III蛋白亚型与TG的关联由apoC-III0a（r = 0.57，p<0.001）、apoC-III0b（r = 0.56，p<0.001）和apoC-III1（r = 0.67，p<0.001）驱动，但与apoC-III2（r = 0.006，p = 0.9）浓度无关，这表明与其他蛋白亚型相比，apoC-III2中apoC-III与血浆TG的关系有所不同。
我们得出结论，apoC-III0a、apoC-III0b和apoC-III1似乎受代谢控制且与空腹血浆TG相关，而apoC-III2并非如此。测量apoC-III蛋白亚型可以深入了解肥胖中TG代谢的生物学机制。
