Increased apoC-III production is a characteristic feature of patients with hypertriglyceridemia

Apolipoprotein (apo) C-III plays an important role in regulating plasma triglyceride (TG) metabolism. In order to further investigate the plasma metabolism of apoC-III in hypertriglyceridemic subjects, we have studied the plasma kinetics of VLDL apoC-III, HDL apoC-III and total plasma apoC-III with a primed constant intravenous infusion of deuterated leucine in a group of male patients with mixed hyperlipidemia (type IIb hyperlipoproteinemia, HLP, n = 6) and in a group with type III HLP (n = 6). Compared to normolipidemic control subjects (n = 5), patients with type IIb and type III HLP had significantly higher levels of plasma TG (0.89 ± 0.15 mmol/l vs 2.56 ± 0.40 mmol/l vs 8.76 ± 1.39 mmol/l, respectively, P< 0.01), plasma apoC-III (9.5 ± 0.8 mg/dl vs 20.8 ± 2.5 mg/dl vs 41.7 ± 5.6 mg/dl, P< 0.01) and VLDL apoC-III (3.6 ± 0.8 mg/dl vs 14.6 ± 2.2 mg/dl vs 35.4 ± 5.1 mg/dl, P< 0.01). VLDL apoC-III production rates were significantly elevated in type IIb and type III patients (1.35 ± 0.23 mg kg−1 day−1 vs 3.53 ± 0.43 mg kg−1 day−1 vs 5.60 ± 0.78 mg kg−1 day−1, P< 0.01), as were total plasma apoC-III production rates (1.80 ± 0.22 mg kg−1 day−1 vs 4.16 ± 0.44 mg kg−1 day−1 vs 7.26 ± 0.74 mg kg−1 day−1, P< 0.01). VLDL apoC-III but not total plasma apoC-III fractional catabolic rates were reduced in type IIb and type III patients. Together with our previous results showing an increase of apoC-III production in patients with type IV HLP, and in overweight subjects with reduced insulin sensitivity, our data suggest that increased apoC-III production is a characteristic feature of patients with hypertriglyceridemia.