Effect of fasting and feeding on apolipoprotein A-I kinetics in preβ1-HDL, α-HDL, and triglyceride-rich lipoproteins

Abstract

The aim of this study was to compare the kinetics of apolipoprotein (apo)A-I during fed and fasted states in humans, and to determine to what extent the intestine contributes to apoA-I production. A stable isotope study was conducted to determine the kinetics of apoA-I in preβ₁ high-density lipoprotein (HDL) and α-HDL. Six healthy male subjects received a constant intravenous infusion of ²H₃-leucine for 14 h. Subjects in the fed group also received small hourly meals. Blood samples were collected hourly during tracer infusion and then daily for 4 days. Tracer enrichments were measured by mass spectrometry and then fitted to a compartmental model using asymptotic plateau of very-low-density lipoprotein (VLDL) apoB100 and triglyceride-rich lipoprotein (TRL) apoB48 as estimates of hepatic and intestinal precursor pools, respectively. The clearance rate of preβ₁-HDL-apoA-I was lower in fed individuals compared with fasted subjects (p < 0.05). No other differences in apoA-I production or clearance rates were observed between the groups. No significant correlation was observed between plasma apoC-III concentrations and apoA-I kinetic data. In contrast, HDL-apoC-III was inversely correlated with the conversion of α-HDL to preβ₁-HDL. Total apoA-I synthesis was not significantly increased in fed subjects. Hepatic production was not significantly different between the fed group (17.17 ± 2.75 mg/kg/day) and the fasted group (18.67 ± 1.69 mg/kg/day). Increase in intestinal apoA-I secretion in fed subjects was 2.20 ± 0.61 mg/kg/day. The HDL-apoA-I kinetics were similar in the fasted and fed groups, with 13% of the total apoA-I originating from the intestine with feeding.

Figure 1

Evolution of main lipid parameters during the kinetic protocols. The white circles indicate the fasted sate and the grey circles indicate the feeding state. Values represent means ± SD for six subjects. *p < 0.05; **p < 0.01 (Wilcoxon matched-pairs signed rank test).

Figure 2

Enrichment of plasma leucine (A), VLDL-apoB100 (B), preβ₁-HDL-apoA-I (C) and α-HDL-apoA-I (D) with deuterated leucine during the fasted (white circles) and fed state (grey circles) over 14 h or 96 h. Values represent means ± SD for six subjects.

Figure 3

Enrichment of TRL-apoB48 with deuterated leucine during the fed state. Values represent means ± SD for six subjects.

Figure 4

ApoA-I tracer/tracee ratios within TRL, preβ₁-HDL and α-HDL fractions after a constant deuterated leucine infusion in a representative subject in a fed state.

Figure 5

Multi-compartmental model used to analyze kinetics of apolipoprotein A-I (apoA-I) in the fasting (A) and the fed (B) states.