© 1997 American Heart Association, Inc.
Articles |
Postprandial Elevation of ApoB-48-Containing Triglyceride-Rich Particles and Retinyl Esters in Normolipemic Males Who Smoke
From the Department of Internal Medicine, Division of Endocrinology and Diabetes, University of Helsinki, Finland (N.M., M.S., M.-R.T.); and the Department of Internal Medicine, University of Gothenburg, Sweden (B.E., U.S.).
Correspondence to Prof. Marja-Riitta Taskinen, Department of Medicine, University of Helsinki, Haartmaninkatu 4, FIN-00290 Helsinki, Finland.
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Abstract |
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Abstract Smokers have an increased risk for coronary artery disease (CAD), which can only partly be explained by fasting lipoprotein changes. Recent studies have indicated that smokers express metabolic abnormalities characteristic of insulin resistance syndrome. A preliminary study reported an increased postprandial triglyceride (TG) response in smokers compared with nonsmokers. To investigate the effect of smoking on postprandial lipemia, a fat-rich mixed meal (837 kcal, 63 g of fat) was served to 12 healthy smokers and 12 controls with similar fasting lipoprotein profiles, body composition, and lifestyles. Blood was drawn before and 3, 4, 6, and 8 hours postprandially, and triglyceride-rich lipoprotein (TRL) fractions (chylomicrons, VLDL1, VLDL2, and IDL) were separated with density gradient ultracentrifugation. Pre- and postprandial TG, retinyl esters (RE), apolipoprotein B-48 (apoB-48) and B-100 (apoB-100) were measured in each fraction. Smokers showed a significantly increased postprandial TG response in chylomicrons, VLDL1, and VLDL2. The areas under the incremental curve (AUIC) of apoB-48 in chylomicrons (2.83±0.84 versus 0.56±0.17; P<.05) and VLDL1 (10.17±1.96 versus 2.95±2.44; P=<.01) were markedly higher in smokers than in controls. Changes of RE responses of all TRL fractions were consistent with those of apoB-48. Postprandial apoB-100 concentrations and lipolytic enzymes were similar between the two groups. In conclusion, smokers have the syndrome of impaired TG tolerance because of defective clearance of chylomicrons and their remnants. Prolonged residence time of atherogenic remnant particles may constitute a significant risk factor for CAD in smokers.
Key Words: smoking • triglyceride-rich lipoproteins • apoB-48 • postprandial lipemia • coronary artery disease
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Introduction |
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Smoking is a well recognized risk factor for coronary artery disease (CAD).1 2 3 A recent meta-analysis of available studies highlighted interactions between smoking and serum lipoprotein concentrations.4 Smokers have elevations of triglycerides (TG), serum and LDL cholesterol, as well as decreases of HDL cholesterol and apolipoprotein (apo)A-I compared with nonsmokers. Evidence for a possible causality is the dose-dependent relationship between the magnitude of atherogenic lipid and lipoprotein abnormalities and smoking habits. However, fasting plasma lipoprotein changes may at best explain only 8% to 10% of the increased CAD risk in heavy smokers.4
Recently, low insulin sensitivity has been linked to smoking in a dose-dependent manner, and smokers express multiple features of the insulin resistance syndrome.5 6 As in smokers, the fasting lipoprotein profile in insulin resistance syndrome consists of hypertriglyceridemia and a low HDL cholesterol level, which co-exist with enhanced postprandial lipemia and a high concentration of atherogenic small dense LDL.7 8 Axelsen et al9 reported an abnormally large postprandial lipid response to a mixed meal, indicating "fat intolerance" in smokers. However, they only reported responses of plasma TG concentrations in a small cohort, and consequently, the results are considered to be preliminary.
The concept that atherosclerosis is a postprandial phenomenon was introduced by Zilversmit10 more than 15 years ago. Recently, convincing evidence11 12 was accumulated to revive this tenet that Miesenböck and Patsch13 renominated as "triglyceride intolerance." Because postprandial lipemia comprises a heterogeneous group of particles with varying origin, size, and composition, the question is which particle is the atherogenic one?14 To discover the mechanism underlying the association between postprandial lipemia and atherogenesis, both exogenous and endogenous triglyceride-rich lipoprotein (TRL) particles must be measured. Direct quantification of chylomicrons and their remnants can be achieved by the specific determination of apoB-48, which is incorporated into chylomicrons in the enterocytes and carried with the particle and its remnant through the metabolic cascade.15 Chylomicron and remnant metabolism can also be studied by using vitamin A as a marker.16 Retinyl esters (RE) are transported in chylomicrons and in their remnants from the intestine into the liver.
The aim of the study contained herein was to investigate postprandial lipemia after an oral fat load in normolipidemic smokers compared with nonsmoking males. Our specific objective was to define whether exogenous or endogenous TRL particles cause fat intolerance in smokers. We measured both apoB-48 and apoB-100 containing particles in TRL fractions separated by density gradient ultracentrifugation and compared this data with TG and RE measurements in the same fractions.
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Methods |
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Subjects
The study population consisted of 12 males who habitually smoke cigarettes and 12 males who do not smoke. These nonsmoking men were selected to have a similar age range, body mass index, and fasting TG and HDL cholesterol concentrations as the smokers at a screening visit. The smokers were recruited via a newspaper advertisement and nonsmokers from the hospital staff. All subjects were healthy and used no medications. Thyroid, renal, and liver diseases were excluded by routine laboratory tests. Diabetes was excluded according to the World Health Organization's criteria and an oral glucose tolerance test.17 All volunteers had apoE phenotyping and only subjects with apoE 2/3 or apoE 3/4 phenotypes were eligible for the study. The subjects were interviewed by the same investigator about lifestyle factors, and the number of cigarettes smoked per day was recorded. Most subjects practiced some leisure physical activity, and no one consumed a special diet. The subjects' characteristics are shown in Table 1
. Each subject gave his informed
consent, and the study protocol was approved by the Ethics Committee of
Department of Medicine, Helsinki University Central Hospital.
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Oral Fat-Load Test
Blood samples were drawn from an indwelling catheter placed in a
forearm vein at 7:30 AM after the subjects had fasted and
abstained from smoking for 12 hours and from alcohol intake for at
least 2 days. A fat-rich mixed meal consisting of bread, butter,
cheese, sliced sausage, a boiled egg, fresh paprika, soured whole milk,
orange juice, and coffee was served to the subjects. The meal contained
63 g of fat, 490 mg of cholesterol, with a P/S ratio
of 0.08, 25 g of carbohydrate, and 35 g of protein. 150 000
IU of vitamin A was administered during the meal. Postprandial blood
samples were drawn at 3, 4, 6, and 8 hours after the fat load. Venous
blood was collected into tubes containing EDTA, and plasma was
separated within 20 minutes by low-speed
centrifugation. Samples were protected from light and
kept at +4°C before and after centrifugation. After
the test meal, the participants were allowed to take nothing except
water until the last sample. Exertion was not allowed during the test.
Smokers were prohibited from smoking until the 8-hour sample had been
drawn.
Density Gradient Ultracentrifugation
The density of plasma samples used for density gradient
ultracentrifugation was adjusted to d=1.10
kg/L with saline, and preservatives (50 KIE/mL aprotinin and
1 mmol/L phenylmethyl sulfonyl fluoride) were
added. Four milliliters of plasma was placed in 13.4-mL tubes
(Ultra-Clear, Beckman Inc., Palo Alto, Calif) and overlayered carefully
with 3 mL of d=1.065 and d=1.020 kg/L and
2.8 mL d=1.006 kg/L NaCl solutions.
Ultracentrifugation was performed with a SW40 Ti
swinging bucket rotor at 40 000 rotations per minute and at +15°C in
a Beckman Optima LC ultracentrifuge. The Sf>400 fraction
representing chylomicrons was isolated after a run of 32
minutes and collected by aspirating the top 1 mL. The tube was refilled
with d=1.006 kg/L NaCl solution. Thereafter,
ultracentrifugation was continued under the same
conditions and the Sf 60 to 400 fraction (VLDL1) was isolated in a run
of 3 hours 28 minutes. The sample was aspirated and the tube refilled
as previously. To separate the Sf 20 to 60 lipoproteins (VLDL2), IDL
(Sf 12 to 20), LDL (Sf 0 to 12), and HDL, the density gradient
ultracentrifugation was continued for 17 hours and the
fractions were separated as described in detail by Karpe and
Hamsten.18 Aliquots of the isolated fractions were frozen
immediately at -80°C for apoB-48 and apoB-100 determinations.
Measurements of apoB-48 and apoB-100
Concentrations of apoB-48 and apoB-100 were analyzed in
density gradient ultracentrifugation samples from each
smoker and seven control subjects. Briefly, delipidated aliquots of
samples were dissolved in buffer and run in 3.5 to 20%
SDS-polyacrylamide gel electrophoresis according to the method
of Karpe et al19 with slight modifications. Highly
concentrated fasting LDL apoB-100 was used as a standard. Control
samples used for apoB-48 and apoB-100 determinations were prepared from
concentrated nonfasting TRL fraction. Six standard samples ranging from
0.125 to 1 µg of apoB-100 and four control samples were included in
each run. Gels were stained with Coomassie blue G-250 for at least 4
hours and destained in water solution with 7% acetic acid and 12%
methanol for 24 hours. Scanning of gels was performed with a
computer-assisted laser scanning densitometer (Image Quant 3.19,
Molecular Dynamics 1991, Sunnyvale, Calif) at 595 nm. Peaks
representing apoB-48 and apoB-100 were integrated
automatically from the image of the sample, and the measurement was
expressed as the area under the curve (AUC). Concentrations of apoB-48
and apoB-100 were calculated from AUCs with the standard curve.
Intragel and intergel coefficients of variation (CV) for apoB-48 were
3.3% and 13.7% and for apoB-100 CVs were 2.9% and 10.5%,
respectively. The detection limit for apoB-48 and apoB-100 ranged
between 0.01 and 0.02 mg/L.
Analytic Methods
Concentrations of RE, TG, and cholesterol were
analyzed in total plasma and in all lipoprotein fractions. TG
and cholesterol concentrations were measured by automated
enzymatic methods using the Cobas Mira analyzer (Hoffman-La
Roche, Basel, Switzerland). RE levels were measured with
high-performance liquid chromatography as
described by Ruotolo et al.20 ApoB concentrations were
measured from serum samples by an immunoturbidimetric method (Orion
Diagnostica, Espoo, Finland; kit 67249). ApoE phenotyping
was performed in serum by using the method of Havekes et
al.21 Concentrations of glucose, free fatty acids,
insulin, and C-peptide were analyzed in samples obtained during
the fat tolerance test. Insulin and C-peptide were measured by
radioimmunoassay (Kabi Pharmacia Diagnostics AB,
Uppsala, Sweden and Byk-Sangtec Diagnostica GmbH &
Co. KG, Dietzenbach, Germany, kit 323 161, respectively). Baseline
serum nicotine and cotinine concentrations were measured in the smokers
by using gas chromatography as described
previously.22 Quality of laboratory measurements was
controlled with commercial samples for cholesterol
(CV=2.1%), TG (CV=2.2%), apoB (CV=4.4%), and insulin (CV=4.7%). CV
for the RE assay was 9.6% for a low control sample and 9.9% for a
high control sample.
Lipolytic Enzymes
An intravenous bolus injection of heparin (100 IU
per kg of body weight) was given to the subjects at a separate visit at
least one week apart from the fat tolerance test. Blood samples were
drawn before and 15 minutes after the heparin injection into precooled
lithium-heparin tubes. Plasma was separated immediately at +4°C and
stored at -20°C. Plasma lipoprotein lipase (LPL) and hepatic lipase
activities were measured from preheparin and 15-minute
postheparin samples with the method of Huttunen et
al.23
Statistical Analyses
Postprandial TG, RE, apoB-48, and apoB-100 responses were
calculated as AUC and areas under the incremental curve (AUIC) as
described by Matthews et al.24 For each subject, the
parameter measured was plotted against time, and the area
between the zero and 8-hour concentration curve was determined by the
trapezoid rule. Incremental areas were obtained by subtracting the
fasting value from each postprandial value before area
calculation.24 All values are expressed as mean±standard
error of the mean. Statistical differences between the two groups were
calculated with the nonparametric Mann-Whitney U
test. Univariate associations were determined with
Pearson's correlation coefficients. For multiple comparisons, repeated
measures ANOVA was used. To study the independence of between-group
differences, analyses of covariance were performed. We
used age, body mass index, physical activity (hours of exercise per
week and "sedentary" versus "active" classification), alcohol
intake, fasting TG, and apoE phenotype as covariates.
Logarithmic transformations were used where appropriate. The
2 test was used to test between-group differences in
apoE phenotypes.
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Results |
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Serum cotinine levels were >184 ng/mL in the smokers, confirming that they were habitual heavy smokers.25 All subjects had normal fasting glucose levels, and there were no significant differences in postprandial glucose, insulin, or C-peptide levels between the smokers and the nonsmokers (data not shown). The baseline values and postprandial AUC or AUIC of free fatty acids did not differ between the two groups. Fasting LDL (3.75±0.28 versus 3.53±0.36 mmol/L) and HDL cholesterol (1.55±0.13 versus 1.61±0.12 mmol/L) levels were comparable in smokers and nonsmokers.
Postprandial Responses of Triglycerides
The fasting TG concentration was 1.12±0.07
mmol/L (range, 0.78 to 1.62 mmol/L) in control
subjects and 1.10±0.07 mmol/L (range, 0.7 to 1.62
mmol/L) in smokers. The smokers exhibited significantly higher
maximum TG concentration (2.56±0.15 mmol/L; range, 0.98 to
6.98 mmol/L) than nonsmokers (1.50±0.43
mmol/L; range, 0.83 to 2.24 mmol/L;
P=.006). The peak concentration of TG after the fat load
occurred later in smokers than in nonsmokers. The smokers showed slower
decline of TG values after the fat meal. In fact, the TG concentration
at 3 to 6 hours after the fat meal was clearly higher in the smokers
than in the control subjects (P<.05, Kruskal-Wallis). The
TG concentration returned to fasting levels at 6 hours in the
nonsmokers and at 8 hours in the smokers (Fig. 1). Incremental responses (AUIC) of TG in
total plasma, chylomicrons (Sf>400), VLDL1 (Sf 60 to 400), and VLDL2
(Sf 20 to 60) are shown in Table 2.
Smokers had significantly larger AUIC responses of TG in total plasma,
chylomicrons, VLDL1, and VLDL2. By contrast, TG AUC in the IDL (Sf 12
to 20) fraction was significantly larger (0.37±0.04 versus
0.77±0.1 mmol · L-1 · h-1,
P<.001) in the control group; AUIC was comparable in the
two groups. Fasting and postprandial TG levels in the LDL
fraction were similar in smokers and nonsmokers. HDL TG
levels were significantly higher in smokers compared with nonsmokers in
fasting (0.32±0.02 versus 0.27±0.02 mmol/L; P<.05)
samples, but the postprandial values showed no difference.
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) and in controls
(
). Plotted on the y-axis is the concentration and on
the x-axis time in hours after the fatty meal. Data points
are mean; error bars indicate SEM.
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Postprandial Responses of Retinyl Esters
The RE pattern clearly differed from that of TG in both smokers
and nonsmokers. The peak concentration of RE was achieved later than
the maximum concentration of TG in total plasma and each TRL fraction
(Figs 1
and 2). Smokers had significantly
larger RE responses in total plasma, chylomicrons, and VLDL1 than
nonsmokers (Table 3). In contrast,
responses of RE in VLDL2, LDL, or HDL were similar in the two groups.
In IDL fraction, AUC was higher in controls (1.35±0.39 versus
0.64±0.07 µmol · L-1 · h-1;
P=.027), but AUIC did not differ.
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In the fasting samples, most (85%) of the RE (0.71±0.061 µmol/L) was found in LDL (0.605±0.065µmol/L), whereas the HDL fraction contained 0.135±0.013 µmol/L. The postprandial increase of LDL and HDL RE concentrations was similar in the two groups. The peak level of RE was reached at 8 hours (0.792±0.071 µmol/L in LDL and 0.219±0.016 µmol/L in HDL). The change in both LDL and HDL RE concentrations from fasting to peak postprandial levels was significant (P<.0001). However, the TRL fractions carried more than 80% of the RE postprandially.
Postprandial Responses of apoB-48 and apoB-100
In smokers, the apoB-48 concentration in the chylomicron fraction
continued to increase until 6 hours after the fat load compared with 4
hours in the control group (Fig. 3A).
Table 2 specifies the postprandial responses (AUIC) of apoB-48 and
apoB-100 in chylomicron, VLDL1, and VLDL2 fractions. Among smokers, the
apoB-48 response was significantly larger in chylomicrons, VLDL1, and
VLDL2 than in nonsmokers. In contrast, responses of apoB-100 in these
fractions were similar in the two groups (Fig. 3B). The maximum
concentration of apoB-100 in chylomicrons was reached at 6 hours in
both groups. The control group had a significantly larger area (AUC)
for apoB-100 in the IDL fraction (1219.2±219.1
mg · L-1 · h-1) than the smokers
(261.5±36.7 mg · L-1 · h-1;
P<.0001), but the incremental areas were similar. The
apoB-48 concentrations were comparable among the groups in IDL.
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The AUC and AUIC of TG were correlated with the respective measures of apoB-48, apoB-100, and RE in total plasma and chylomicrons (data not shown). We observed a correlation between C-peptide AUIC and plasma TG AUIC (r=0.705; P<.01) and chylomicron TG (r=0.612; P=.05), as well as between C-peptide AUIC and chylomicron apoB-48 AUIC (r=0.651; P=.05) and VLDL1 AUIC (r=0.482; P=.05). In contrast, no association was found between insulin AUIC and the degree of postprandial lipemia. The number of cigarettes smoked per day, serum cotinine concentrations, or the duration of smoking did not show any association with the magnitude of postprandial lipemia or apolipoproteinemia.
Lipase Activities
Postheparin plasma LPL and hepatic lipase activities
as well as the LPL/hepatic lipase ratio were similar in the smokers and
nonsmokers (data not shown). In nonsmokers, we observed an inverse
correlation between plasma TG AUC and postheparin LPL
activity (r=-0.664; P<.05). In contrast, these
parameters did not correlate in smokers (TG AUC versus LPL
r=0.034, NS). Also postheparin LPL activity and
free fatty acid AUC correlated among the control subjects
(r=0.641; P<.05), but not in the smokers
(r=0.281; NS).
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Discussion |
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Our data confirm the preliminary observation of Axelsen et al9 that smokers indeed have "the syndrome of impaired TG tolerance," a concept introduced by Miesenböck et al.26 The present results extend previous findings by showing that smokers exhibit elevations of both postprandial apoB-48 and RE responses. In fact, two independent markers of exogenous TRL particles, RE and apoB-48, were closely correlated with TG responses after an oral fat load. Thus, the data indicate accumulation of chylomicrons and their remnants as the main feature of fat intolerance in smokers. Taken together, the data suggest that the clearance of chylomicrons and their remnant particles is impaired in smokers. We found marked differences between smokers and nonsmokers in the magnitude of postprandial lipemia, despite comparable fasting TG and HDL concentrations in the two groups. Although fasting TG and HDL cholesterol levels are important determinants of postprandial lipemia,27 our data suggest that these factors cannot explain the exaggerated postprandial lipemia in smokers. A high level and a prolonged residence time of atherogenic remnants in circulation could contribute to the high CAD risk of smokers.
ApoB-48 measurement has been a methodologic challenge because of its low concentrations and structural similarity with apoB-100. In this study, the detection limit and CV for the two subspecies of apoB were comparable with those of previous reports.18 28 Retinyl palmitate has commonly been used to trace chylomicrons and remnants. REs are transported in intestinally derived TRL particles to the liver, and they are not re-secreted in VLDL particles.29 We observed a clear correlation between the responses of RE and apoB-48 in chylomicrons and in VLDL1. However, the time of the peak RE concentration did not coincide with that of apoB-48 or TG in chylomicron, VLDL1, or VLDL2 fractions. The data agree well with the results of Karpe et al,19 who speculated that the early dissociation of RE and apoB-48 responses may be the result of variation in the vitamin A absorption, depending on the amount of fat ingested. Another caveat is that RE may exchange between circulating lipoproteins as evidenced by the slow increase of RE in VLDL2, LDL, and HDL fractions. Overall, in our study, RE served as a reasonable tool in the quantification of postprandial levels of intestinally derived particles.
Why is the clearance of chylomicrons and their remnants delayed in smokers? The catabolism of chylomicrons occurs in two major steps: first, lipolysis by LPL, which results in formation of chylomicron remnants; and second, removal of the remnant particles from circulation by the liver via a receptor-mediated pathway. The lipolytic cascade is initiated by the binding of circulating chylomicrons to LPL-heparan sulfate complexes bound to the endothelial wall of peripheral capillaries. Binding affinity of remnant particles to LPL-heparan sulfate complexes varies with particle size; larger particles are considered to be better substrates for LPL.30
Can a lipolytic defect explain the excessive postprandial lipemia in smokers? Of note is that we observed no differences in either pre- or postheparin LPL activity between the two groups. However, this does not exclude a lipolytic defect. If lipase activity is sufficient but the interaction between the TRL particles and LPL at the capillary endothelium is abnormal, the lipolytic process will be impaired. We observed an inverse correlation between LPL activity and postprandial TG AUC in the controls, as expected, but not in the smokers. Similarly, in two recent studies of postprandial lipemia in patients with noninsulin-dependent diabetes and in diabetic and nondiabetic CAD patients, there was a lack of correlation between LPL and postprandial TG responses.31 32 We observed no differences in postprandial free fatty acids responses, but again the association between LPL and free fatty acids AUC found in the control group was lost in the smokers.
In the IDL fraction, we found larger TG and apoB-100 AUCs in nonsmokers than in smokers. This may seem paradoxical, as IDL is considered an atherogenic lipoprotein.33 We previously found a similar excess of RE in the IDL fraction of healthy control subjects compared with CAD patients and diabetic patients32 and speculated that impaired lipolysis might explain the lower levels of postprandial lipemia in the IDL fraction in the patient groups. The same line of reasoning would imply that in nonsmokers, the lipolytic cascade works more efficiently than in smokers, resulting in higher concentrations of IDL in the former group. In smokers, on the other hand, processing of TRLs seems to be impaired, possibly resulting in excessive removal of the lipoproteins via shunt pathways34 and deposition of these partially lipolyzed remnants in the arterial wall.
A defect in clearance of exogenous remnant particles by the liver is another potential explanation of fat intolerance in smokers. Indeed, we observed accumulation of Sf 60 to 400 and Sf 20 to 60 apoB-48-containing particles. The hepatic removal process of exogenous TRL particles and, maybe also, large VLDL species involves the apoE-dependent LDL receptor-related protein (LRP), whereas small VLDL remnants and IDL are thought to be cleared mainly through the LDL receptor (35). Recently, LPL was recognized as having a role also in chylomicron remnant clearance. This action is independent of the catalytic activity of the enzyme.35 36 If this LDL receptor-related protein-mediated removal of apoB-48-containing particles is disturbed in smokers, the result would be an elevation in the level of apoB-48-containing particles, as we observed in the present study. Although our study does not allow conclusions about the putative remnant removal defect in smokers, one can speculate that smoking might impair the interaction between remnants and hepatic receptors, but the mechanisms underlying such a defect are unknown at present.
Controversial data exist regarding the effect of apoE phenotype in TRL clearance. Weintraub et al37 reported enhanced clearance of dietary fat in apoE 3/4 heterozygotes. On the other hand, a recent publication by Bergeron and Havel38 suggested prolonged metabolism of intestinal and hepatogenous TRL remnants in young men with apoE 3/4 phenotype compared with apoE 3/3 subjects. In the study presented herein, only three subjects in the smoking group had apoE phenotype 3/4. When individuals with apoE 3/3 phenotype were analyzed separately, the differences in postprandial apoB-48, apoB-100, RE, and TG responses persisted (data not shown).
Cigarette smoking induces multiple endocrine and neurohumoral effects, including elevations of cathecolamine, growth hormone, cortisol, and insulin levels, which in turn might cause changes in lipolytic enzymes and in lipoprotein metabolism in the liver, but the detailed mechanisms of most of these interactions are unknown.39 40 A growing body of data indicates that smokers are insulin-resistant. Recently, fat intolerance was recognized as an inherent feature of insulin resistance syndrome.7 However, in the present study, smokers had similar fasting and postprandial glucose, e-peptide, and insulin concentrations as control subjects. An oral glucose tolerance test was performed in the smoking group to exclude impaired glucose tolerance, which strongly enhances postprandial lipemia. Thus, we cannot explain the fat intolerance in the smokers by insulin resistance.
The study groups are relatively small because of the demanding methodology, and, therefore, possible confounding factors must be taken into consideration. Nonsmokers in this study showed a reasonably low postprandial TG response, and this raises the question: Are our nonsmokers somehow unusual? The nonsmokers represent average lean and healthy males. There was a tendency toward a more sedentary lifestyle, higher body mass index, and slightly higher alcohol intake in the smokers. However, these differences in lifestyle factors were not statistically significant. Of note is that despite differences in lifestyle the two groups had similar fasting TG and HDL-cholesterol concentrations, which are known to have a major influence on postprandial lipemia.27 The postprandial difference between smokers and nonsmokers is remarkable, and the peak TG and apoB-48 concentrations differ clearly; thus, we cannot explain these differences by trivial lifestyle variation between the groups. The accumulation of TRL particles containing apoB-48 but not apoB-100 in smokers could result from slow gastric emptying of solids and delayed absorption of dietary fat,41 but this should only alter the temporal sequence of the lipid response and should not affect the magnitude of postprandial lipemia if the clearance system functions normally. In the study contained herein, increases of TG, RE, and apoB-48 in the smokers were evident already at 3 hours after the fat load. Thus, the early phase of the lipemic response was exaggerated, but the return to the baseline level was also delayed in smokers, suggesting disturbed catabolism of postprandial lipids.
Many clinical studies have suggested that remnants of TRLs are atherogenic.42 43 Groot et al11 and Patsch et al44 showed that CAD patients had elevated and prolonged postprandial TG responses compared with control subjects, independently of fasting TG levels. In the present study, the postprandial TG response was significantly increased and the peak TG levels were delayed in smokers compared with nonsmokers. We were able to demonstrate that these differences were the result of an accumulation of intestinally derived chylomicrons and chylomicron remnants. We conclude that even in the absence of fasting dyslipidemia, the disturbance of postprandial lipid metabolism may constitute a significant risk factor for atherosclerosis in smokers.
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Selected Abbreviations and Acronyms |
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Acknowledgments |
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We gratefully acknowledge the excellent laboratory work by Hannele Hilden, Leena Lehikoinen, Ritva Marjanen, Helinä Perttunen-Nio and Sirpa Rannikko. We thank Maaria Puupponen for excellent secretarial assistance and Soile Aarnio for drawing the figures. The nicotine and cotinine analyses were kindly performed by Pharmacia Sweden AB, Helsingborg, Sweden.
Received June 11, 1996; accepted July 2, 1997.
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References |
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