Atherosclerosis 151 2000 381 – 388
Effects of age, gender, and lifestyle factors on plasma apolipoprotein A-IV concentrations
Zhiyong Sun
a
, Ilona A. Larson
a
, Jose M. Ordovas
a
, James R. Barnard
b
, Ernst J. Schaefer
a,
a
Lipid Metabolism Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts Uni6ersity,
711
Washington Street, Boston, MA
02111
, USA
b
Department of Medicine, Laboratory of Kinesiology, Di6ision of Clinical Nutrition, Uni6ersity of California, Los Angeles, CA, USA Received 17 February 1999; received in revised form 31 August 1999; accepted 15 September 1999
Abstract
Apolipoprotein apo A-IV is a protein component of triglyceride TG-rich lipoproteins and high density lipoproteins HDL. Plasma apo A-IV levels were measured by immunoelectrophoresis and these values were related to other biological variables in
723 middle aged and elderly men and women more than 90 of them were Caucasian prior to participation in a lifestyle modification program. Apo A-IV may play an important function in regulating lipid absorption, reverse cholesterol transport, and
food intake. The data are consistent with the following concepts: 1 apo A-IV levels are significantly and positively correlated with age r = 0.159, P B 0.05 in all subjects, with plasma apo A-I levels in both men r = 0.194, P B 0.001 and women r = 0.213,
P B 0.001, and with apo E r = 0.111, P B 0.05 and TG levels r = 0.120, P B 0.05 in men; 2 apo A-IV levels are inversely correlated with body mass index r = 0.170, P B 0.05 in women; 3 female subjects on hormone replacement therapy have
significantly lower plasma apo A-IV levels by 4.1, P B 0.05 than normal controls; 4 diabetic subjects have significantly higher apo A-IV levels by 21, P B 0.01 than normal subjects; 5 there is no significant effect of smoking, alcohol intake, and apo
A-IV-12 genotype on apo A-IV levels. The data indicate that plasma apo A-IV levels are significantly affected by age, diabetes, and hormone replacement therapy. © 2000 Elsevier Science Ireland Ltd. All rights reserved.
Keywords
:
Lipoprotein; Apolipoprotein A-IV; Population study; Diabetes; Hormone replacement therapy www.elsevier.comlocateatherosclerosis
1. Introduction
Human apolipoprotein apo A-IV is an apolipo- protein synthesized in the intestine. Since its discovery
in the late 1970s [1], many studies have been done to elucidate its physiologic and biochemical functions, ge-
netic variations, and metabolism. The function of this apolipoprotein and its association with disorders such
as coronary heart disease and Alzheimer’s disease are not completely understood. It has been suggested that
apo A-IV may facilitate andor mediate lipid absorp- tion, transport, and utilization. Apo A-IV synthesis and
secretion increase after consuming a meal, especially one high in fat [2 – 4]. Weinberg et al. [5] reported that
plasma apo A-IV concentrations increased with in- creases in dietary fat content, in a dose-dependent
manner. Animal studies have shown stimulation of apo A-IV synthesis in response to graded doses of dietary
fat [6 – 10]. Apo A-IV is a critical protein component of chylomicrons, and when chylomicrons enter the circula-
tion, they exchange apolipoproteins with high density lipoproteins HDL by picking up apo Cs and E from
HDL and donating apo A-IV to HDL [11,12]. Further- more, apo C-II activates lipoprotein lipase LPL en-
abling LPL-mediated TRL lipid hydrolysis, while apo E binds to specific receptors in the liver and other organs
to facilitate TRL particle clearance. Apo A-IV may also participate in reverse cholesterol transport RCT. It
has been proposed that apo A-IV is involved in RCT by
activating lecithin:
cholesterol acyltransferase
LCAT [13 – 15], enhancing cholesterol ester transfer protein CETP activity [16], and facilitating cholesterol
Corresponding author. Tel.: + 1-617-556-3100; fax: + 1-617-556- 3103.
E-mail address
:
eschaeferhnrc.tufts.edu E.J. Schaefer 0021-915000 - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0 0 2 1 - 9 1 5 0 9 9 0 0 3 9 5 - 0
efflux from cells in different tissues into HDL [17 – 19]. Data also exists suggesting that apo A-IV may be
involved in the regulation of food consumption [20]. Studies in rats have documented that apo A-IV infusion
and injection can reduce food intake [21 – 23]. While the physiological mechanism of this effect is not clear, it
has been suggested that apo A-IV may enter the central nervous system CNS to perform this function. Both
serum and cerebrospinal fluid apo A-IV levels increase markedly as a result of lipid consumption [22 – 24]. Apo
A-IV may inhibit gastric acid secretion in rats and reduce the severity of gastric ulceration by a mechanism
involving the CNS [25,26]. Moreover, in a transgenic study by Duverger et al. [27], it was reported that apo
A-IV had arteriosclerosis-protective potential in human apo A-IV gene transgenic mice. In another transgenic
mouse study by Qin et al. [28], an antioxidant function of apo A-IV was noted.
The effects of age, gender, and lifestyle factors smoking, alcohol consumption, and use of medication
for diabetes, cholesterol-lowering, thyroid disease, or hormone replacement therapy on human plasma apo
A-IV have not been well studied. Available data on relationships between plasma apo A-IV and various
physiological parameters age, gender, BMI, percent body fat, girth, blood glucose, and lipid levels are
reviewed in this manuscript. Elucidating such effects and relationships is helpful for understanding lipid
metabolism and its links to coronary heart disease CHD. Thus far, little is known about the relationship
between apo A-IV and other apolipoproteins, how life style influences apo A-IV levels, and what impact
healthmedication status has on plasma apo A-IV lev- els. In order to further elucidate apo A-IV physiology,
the influences of biological variables on human plasma apo A-IV levels were assessed in 723 participants in the
present study.
2. Subjects and methods
