Key result
Feeding significantly lowered the clearance rate of preβ1-HDL-apoA-I compared to fasting (0.235 vs 0.447 pool/day, p=0.045), with no other major differences in apoA-I production or clearance.
Why the study?
To compare the kinetics of apolipoprotein (apo)A-I during fed and fasted states in humans and determine the extent to which the intestine contributes to apoA-I production.
Does feeding alter the kinetics of apolipoprotein A-I in preβ1-HDL and α-HDL compared to fasting in healthy male subjects?
RCT (n=6)
Open-label
Randomized crossover
No
Does feeding alter the kinetics of apolipoprotein A-I in preβ1-HDL and α-HDL compared to fasting in healthy male subjects?
Feeding decreases the clearance rate of preβ1-HDL-apoA-I but does not significantly alter overall apoA-I synthesis or catabolism, with the intestine contributing approximately 13% of total apoA-I production.
Feeding status merits standardization in apoA-I kinetic protocols; leaves open any impact on HDL function or cardiovascular risk.
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 preβ 1 high-density lipoprotein (HDL) and α-HDL. Six healthy male subjects received a constant intravenous infusion of 2 H 3 -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 preβ 1 -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 preβ 1 -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.
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Chétiveaux et al. (2020) conducted an RCT in Healthy (n=6). Feeding (small hourly meals) vs. Fasting was evaluated on Preβ1-HDL-apoA-I fractional catabolic rate (FCR) (p=0.045). Feeding significantly lowered the clearance rate of preβ1-HDL-apoA-I compared to fasting (0.235 vs 0.447 pool/day, p=0.045), with no other major differences in apoA-I production or clearance.
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