The Association of Human Apolipoprotein C-III Sialylation Proteoforms with Plasma Triglycerides

INTRODUCTION: Apolipoprotein C-III (apoC-III) regulates triglyceride (TG) metabolism. In plasma, apoC-III exists in non-sialylated (apoC-III(0a) without glycosylation and apoC-III(0b) with glycosylation), monosialylated (apoC-III(1)) or disialylated (apoC-III(2)) 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-III(0a), apoC-III(0b), and apoC-III(1) to apoC-III(2) 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 (S(i)). The relationship of apoC-III(1) / apoC-III(2) with S(i) persisted after adjusting for BMI (p = 0.02). Fasting TG was correlated with the ratio of apoC-III(0a) / apoC-III(2) (r = 0.47, p<0.001), apoC-III(0b) / apoC-III(2) (r = 0.41, p<0.001), apoC-III(1) / apoC-III(2) (r = 0.43, p<0.001). By examining apoC-III concentrations, the association of apoC-III proteoforms with TG was driven by apoC-III(0a) (r = 0.57, p<0.001), apoC-III(0b) (r = 0.56. p<0.001) and apoC-III(1) (r = 0.67, p<0.001), but not apoC-III(2) (r = 0.006, p = 0.9) concentrations, indicating that apoC-III relationship with plasma TG differed in apoC-III(2) compared with the other proteoforms. CONCLUSION: We conclude that apoC-III(0a), apoC-III(0b), and apoC-III(1), but not apoC- III(2) 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.