Effect of body mass index on apolipoprotein A-I kinetics in middle-aged men and postmenopausal women

doi:10.1016/j.metabol.2007.01.022

Metabolism

Volume 56, Issue 7, July 2007, Pages 910-914

https://doi.org/10.1016/j.metabol.2007.01.022 Get rights and content

Abstract

The effect of body mass index (BMI) and obesity on apolipoprotein (apo) A-I levels and kinetics was examined by gender. Apo A-I kinetics were determined with a primed, constant infusion of deuterated leucine in the fed state in 19 men and 13 postmenopausal women. Compared with nonobese men, nonobese women had a higher level of high-density lipoprotein cholesterol (HDL-C) and apo A-I due to a 48% higher apo A-I production rate (PR) (P = .05). Obesity had no significant effects on apo A-I kinetics in women. In contrast, compared with nonobese men, obese men had a 9% lower apo A-I level due to a 64% higher fractional catabolic rate (FCR) partially offset by a 47% higher PR. Obese women had a 52% higher HDL-C than obese men (50 vs 33 mg/dL, respectively; P = .012), a finding related to the faster apo A-I FCR in obese men. BMI was directly correlated with apo A-I FCR (r = 0.84, P < .001) and PR (r = 0.79, P < .001) in men but not in women. Sixty-two percent of the variability in PR and 71% of the variability in FCR were due to BMI in men and only 3% and 23%, respectively, in women. In conclusion, BMI has a significant effect on apo A-I PR and FCR in men but not in women.

Introduction

High levels of high-density lipoprotein cholesterol (HDL-C) have been associated with lower rates of coronary heart disease in epidemiologic studies [1]. The plasma level of apolipoprotein (apo) A-I, the major protein of atheroprotective HDL, is higher in both pre- and postmenopausal women compared with men [2]. The reasons for this are not entirely clear. A prior meta-analysis of 13 stable isotope studies examined the effect of obesity on apo A-I kinetics but did not report results by sex [3]. Two prior studies, using stable isotopes, have reported on sex differences in kinetics of apo A-I but did not have a large enough sample size to examine the effect of obesity by sex on kinetics [4], [5]. Using stable isotopes in the current study, we added obese subjects to the prior 2 studies and used multicompartmental modeling to examine the effect of body mass index (BMI) and obesity on the apo A-I fractional catabolic rate (FCR) and production rate (PR) in obese and nonobese middle-aged men and women.

Section snippets

Methods

Subjects for these studies were 19 men and 13 postmenopausal women stratified in relation to obesity as defined by a BMI of 30 kg/m² or greater. We added 2 obese men, 3 obese women, and 4 nonobese women to the previously published subjects [4], [5]. All subjects received a primed, constant infusion of [²H₃]leucine intravenously at 10 μmol/kg per hour for 15 hours while consuming small hourly meals, as previously described [4], [5], [6], [7], [8]. Lipoproteins were isolated by sequential density

Results

The group averages of age, BMI, and lipid levels of the subjects are shown in Table 1. The obese men were an average of 13 years younger than the obese postmenopausal women (P = .05), but there was no significant difference in BMIs (31 vs 33 kg/m²). Two sets of comparisons were performed. The first comparison was the effect of sex by obesity status (Table 2). Compared with nonobese men, nonobese women had a 42% higher level of HDL-C (43 ± 9 vs 61 ± 20 mg/dL, respectively; P = .006) (Table 1)

Discussion

In the current study, nonobese women had a higher HDL-C level than nonobese men due to a 48% higher apo A-I PR. Because these women were postmenopausal, this sex difference cannot be attributed to higher estrogen levels but is more likely due to the presence of testosterone in men, which has been shown to lower HDL-C because of decreased production of apo A-I at puberty [12].

When we examined the effect of obesity on HDL-C levels and apo A-I kinetics, we found that compared with nonobese men,

Acknowledgments

This study was supported by grants HL 39326 (E.J.S.) and HL56895 (F.K.W.) and contract 53-3KO6-5-10 from the US Department of Agricultural Research Service (E.J.S.).

We are extremely grateful to the study subjects for participating in the kinetics studies.

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Effect of body mass index on apolipoprotein A-I kinetics in middle-aged men and postmenopausal women

Abstract

Introduction

Section snippets

Methods

Results

Discussion

Acknowledgments

J Lipid Res

J Lipid Res

Metabolism

Metabolism

Atherosclerosis

High-density lipoprotein: the clinical implications of recent studies

N Engl J Med

High-density lipoprotein apolipoprotein A-I kinetics in obesity

Obesity Res

Impact of gender on the metabolism of apolipoprotein A-I in HDL subclasses LpAI and LpAI:AII in older subjects

Arterioscler Thromb Vasc Biol

Apolipoprotein A-I and A-II kinetic parameters as assessed by endogenous labeling with 2[H]3-leucine in middle aged and elderly men and women

Arterioscler Thromb Vasc Biol

Interrelationships between human apolipoprotein A-I and apolipoproteins B-48 and B-100 kinetics using stable isotopes

Arterioscler Thromb Vasc Biol

Apolipoprotein A-I and A-II kinetic parameters as assessed by endogenous labeling with ²[H]³-leucine in middle aged and elderly men and women