Abstract 17840: Metabolism of Apolipoprotein B Lipoproteins Defined by the Presence of Apolipoprotein C-II and/or Apolipoprotein C-III

Abstract

Background: Apolipoprotein (apo) C-II and apoC-III are synthesized by the liver and associate predominantly on triglyceride (TG) rich lipoproteins (TRL). ApoC-II facilitates lipolysis, by activating lipoprotein lipase (LPL), while apoC-III may inhibit this pathway. No studies, however, have examined apoB kinetics according to the presence of apoC-II. To elucidate the role of apoC-II in cardiovascular disease, it is fundamental to understand its impact on lipoprotein metabolism in vivo. Objective: We examined the metabolism of apoB-containing lipoproteins, with a focus apoC-II and apoC-III.

Methods: We studied apoB kinetics within 20 distinct subfractions separated by anti-apoC-II and anti-apoC-III immunoaffinity chromatography and ultracentrifugation in 12 subjects (7 men and 5 women, mean ± SD: age 53 ± 11 yrs, BMI 28.4 ± 5.1 kg/m², plasma TG 2.1 ± 1.0 mmol/L, LDLC 3.2 ± 0.6 mmol/L, HDLC 1.3 ± 0.7 mmol/L).

Results: We found that 7% of plasma TRL (VLDL and IDL) contained apoC-II (apoCII+) and of these, 20% had no apoC-III (apoCII+/apoCIII-). The proportion of TRL with apoC-III (apoCIII+) was 51% and of these, 89% had no apoC-II (apoCII-/apoCIII+). On average, VLDL apoCII+/apoCIII- production rate (PR) and fractional catabolic rate (FCR) were significantly lower than that of VLDL apoCII-/apoCIII+ (Mean ± SEM, PR: 0.02 ± 0.01 vs. 1.70 ± 0.23 mg/kg/d, p<0.01 and FCR: 1.70 ± 0.87 vs. 5.83 ± 0.86 pools/d, p<0.01). Similarly, IDL apoCII+/apoCIII- PR was significantly lower than that of IDL apoCII-/apoCIII+ (0.04 ± 0.02 vs. 2.39 ± 0.10 mg/kg/d, p<0.01). All (100%) TRL apoCII+/apoCIII- (VLDL to IDL, and to light LDL) were converted down the lipolytic pathway. By contrast, the conversion of VLDL to IDL, and to light LDL apoCII-/apoCIII+ were 89 ± 6% and 22 ± 6%, respectively.

Conclusions: Our results suggest that only a small proportion of TRL apoB particles produced contained apoC-II, but not apoC-III. TRL particles containing apoC-II favored the lipolytic pathway. This may reflect its role as a co-activator of LPL. Conversely, apoC-II may inhibit apoE- and apoB-mediated binding to the LDL receptor (LDLR) and LDLR related protein, thereby impeding TRL and remnant clearance. Our study shows that apoC-II plays a key role in determining the metabolic fate of TRL apoB particles.