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*
Human Nutrition Unit, School of Molecular and Microbial Biosciences, University of Sydney, Sydney, NSW 2006 and
Cell Biology Group, Heart Research Institute, Camperdown, NSW 2050, Australia
2To whom correspondence should be addressed. E-mail: S.Samman{at}biochem.usyd.edu.au.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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KEY WORDS: • trans fatty acids • lipoproteins • rats • kinetics
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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–3
). Numerous well-controlled human trials have shown that dietary TFA, compared with oleic acid, negatively affect the plasma lipoprotein profile by increasing LDL cholesterol (LDL-C) (4
–7
) and lipoprotein(a) [Lp(a)] concentrations (5
,7
,8
). In addition, high TFA intakes have been shown to reduce the plasma HDL cholesterol (HDL-C) concentration (4
,6
,7
), which is inversely associated with CHD risk.
Although much is known about the effects of TFA on plasma lipoprotein cholesterol concentrations, relatively little is known about the underlying mechanisms of action. A limited number of studies (9
,10
) do not support the notion that the effect is mediated via downregulation in LDL-receptor activity. Rather, studies in humans (11
,12
) and nonhuman primates (13
) suggest that the ratio of LDL-C:HDL-C is elevated due to an increase in plasma cholesteryl ester transfer protein (CETP) activity, which results in a greater rate of transfer of cholesteryl esters from HDL to lower density lipoproteins.
The presence of plasma CETP activity varies across the animal kingdom (14
). Humans possess high CETP activity, whereas rats are devoid of transfer activity (14
,15
). In view of the effect of dietary TFA on CETP in humans and nonhuman primates, the aim of the present study was to test the hypothesis that TFA do not negatively affect the plasma lipoprotein profile of animals lacking CETP activity. Differences exist in lipoprotein metabolism between rats and humans. In contrast to humans, rats transport the majority of endogenous cholesterol via HDL, and excessive cholesterol intake results in the production of ß-VLDL. Nevertheless, we employed the rat model primarily due to the absence of CETP to compare the effects of dietary oleic acid (CIS diet), palmitic acid (SAT diet) and TFA (TRANS diet) on plasma lipid and lipoprotein concentrations.
Epidemiologic studies have clearly demonstrated that plasma HDL-C concentrations are inversely associated with the development of CHD (16
–18
). The antiatherogenicity of HDL is thought to be conferred by its participation in reverse cholesterol transport (RCT), the process whereby cholesterol from extrahepatic tissues is transported via the plasma compartment to the liver for excretion as bile acids or redistribution to extrahepatic tissues (19
). Furthermore, recent evidence suggests that the dietary fatty acid composition can exert differential effects not only on the plasma HDL-C concentration, but also on the capacity of HDL to accept cellular cholesterol in vitro (20
,21
). Because the physicochemical properties of TFA are intermediate to those of cis unsaturated and saturated fatty acids (22
), a second aim was to examine the effect of these diets on the ability of HDL to accept cellular cholesterol.
We conducted an in vivo assay of RCT in rats by using [3H]-cholesterol delivered in a high uptake form of LDL. We sought to label the reticuloendothelial system of rats by the intravenous administration of acetylated LDL (acLDL) labeled with [3H]-cholesteryl oleate. The vehicle, acLDL, is a high uptake modified lipoprotein that is rapidly internalized by cells in vitro (23
) and in vivo (24
,25
). The exchange of label between lipoproteins and tissue before uptake is minimized by using steryl esters (located in the core of the particle) and rats, an animal model that lacks CETP (15
). Labeled cholesterol is transported from endothelial cells to parenchymal cells, via RCT, and [3H]-cholesterol is recovered in plasma, mainly in the HDL fraction (24
). The use of this model has provided in vivo evidence that HDL serve as acceptor particles for cholesterol from endothelial cells (24
).
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MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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240 g were purchased from the Combined Universities Laboratory Animal Services and assigned to 3 groups according to body weight. Rats were allowed unrestricted access to water and fed semipurified diets (375 kJ/d) for 4 wk. The diet composition is described below. They were housed in groups of 4 except after surgery when they were housed individually. The animal house was maintained at 20–22°C with a 12-h light:dark cycle (lights on, 0600 h). To determine the effects of diet on plasma lipids and lipoproteins, 10 rats from each group were killed by CO2 gassing, and blood was collected from the abdominal vena cava into tubes containing EDTA (1 mmol/L). For the in vivo assay of RCT, the remaining 12 rats from each group underwent bilateral jugular cannulation and administration of [3H]-cholesterol labeled acLDL. Blood was sampled at timed intervals to evaluate the reappearance of label in plasma and HDL. Livers were removed for the determination of hepatic lipid and radioactive concentrations.
Diets.
The diets comprised 20% energy from protein (casein), 46% energy from carbohydrate (cornstarch/sucrose, 5:1), 35% energy from fat, 10 g/100 g vitamins and minerals, 5 g/100 g cellulose, 0.2 g/100 g cholesterol and 0.2 g/100 g DL-methionine. Detailed composition of the vitamins and minerals mix was reported previously (26
). The fatty acid composition of the diets (Table 1)
differed such that 10% energy was provided as oleic acid in the CIS diet, palmitic acid in the SAT diet or a mixture of monounsaturated trans fatty acids in the TRANS diet. The oil used in the CIS diet was a blend of palm olein, canola, olive, Sunola and fully hydrogenated canola oils, whereas the oil in the SAT diet was a blend of palm stearin, sunflower, fully hydrogenated canola, linseed and Sunola oils. A mixture of partially hydrogenated cottonseed, canola and sunflower oils was used in the TRANS diet.
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), analyzed by gas chromatography and identified by comparison with FAME standards (Nu-Check-Prep, Elysian, MN). FAME were first analyzed using a fused carbon-silica capillary column (phase:cyanopropylphenol, 25 µm; column: 30 m x 0.25 mm; type DB-225, J & W Scientific, Folsom, CA). The proportion of trans isomers was then determined after further chromatography using a stationary phase capillary column (phase: BPX70, 0.25 µm; column: 60 m x 0.22 mm; SGE Australia Pty, Victoria, Australia).
Plasma and hepatic lipid analyses.
Plasma total cholesterol and HDL-C concentrations were determined in rats fed their respective diets for 4 wk. Total cholesterol concentrations were determined enzymatically (Cholesterol CHOD-PAP, Boehringer Mannheim, Ryde, NSW, Australia) using an automated system (Cobas Fara II, Roche Diagnostic Systems, Sydney, NSW, Australia). HDL-C was determined after the precipitation of apolipoprotein (apo) B–containing lipoproteins in the presence of dextran sulfate and magnesium ions (28
). Non-HDL-C was calculated by difference. To investigate further the distribution of cholesterol within apo B–containing lipoproteins, aliquots of plasma from rats in the same group were pooled such that 4 pooled plasma samples were obtained per diet group. Lipoproteins were then isolated by sequential ultracentrifugation with VLDL isolated at d < 1.006 kg/L, intermediate density lipoprotein (IDL) at 1.006 < d < 1.019, LDL at 1.019 < d < 1.063 and HDL at 1.063 < d < 1.21 (29
).
To determine the fatty acid composition and concentration of HDL phospholipids, HDL samples obtained by ultracentrifugation were fractionated into neutral lipids and phospholipids by column chromatography (30
). The fatty acid composition of HDL phospholipids was determined as described above. The phospholipid concentration of HDL was measured by enzymatic assay (Phospholipids, Boehringer Mannheim).
To determine the hepatic radioactive concentration and the proportions of radioactivity associated with free cholesterol and cholesteryl ester, lipid was extracted (31
) and redissolved in chloroform. The hepatic radioactive concentration was analyzed by placing an aliquot of the hepatic lipid extract into scintillation vials and drying under nitrogen before scintillation counting using a Wallac 1409 Liquid Scintillation Counter (Wallac, Turku, Finland). Hepatic free and esterified cholesterol were separated by TLC (32
) and identified by standards (free cholesterol and cholesteryl palmitate) run on the same plate. Bands corresponding to free and esterified cholesterol were scraped into scintillation vials and the radioactivity determined by scintillation counting as described above.
Kinetic study
Isolation of human LDL.
For production of radiolabeled acLDL, human LDL (1.019 < d < 1.063) was isolated from plasma by single vertical spin density gradient ultracentrifugation (206,000 x g) (33
) followed by a wash centrifugation to remove serum albumin. LDL was isolated and dialyzed overnight against PBS (10 mmol/L PBS; 1 mmol/L EDTA, 4°C). After dialysis, the LDL was sterilized by passing through a 0.45-µm filter and the protein concentration was determined (34
).
Acetylation and radiolabeling of LDL.
LDL was acetylated by the repeated addition of acetic anhydride (0.6 L/100 g LDL protein) (35
). Briefly, an equal volume of saturated sodium acetate was added to the LDL and then fresh acetic anhydride was added in 2-µL aliquots. The reaction was conducted at 4°C in the dark with constant mixing. The acLDL was then dialyzed overnight against PBS (10 mmol/L) containing EDTA (20 µmol/L) and chloramphenicol (310 µmol/L). AcLDL was concentrated using a 10-kDa cut-off centrifugal concentrator (4750 g, 10°C, 30 min; CentriSart I, Sartorius, Goettingen, Germany) and stored in the dark at 4°C. The successful modification of LDL was tested by applying acLDL and native LDL to an agarose gel (1g/100g) with barbitol buffer and running at 90 V for 45 min. The gel was fixed in methanol and then stained with Fat Red 7B for 15 min. Satisfactory acetylation was defined as a relative electrophoretic mobility of > 3 (36
). The relative electrophoretic mobility was determined to be 4.3, indicating that the acetylation of LDL was successful.
Incorporation of radiolabeled cholesteryl ester into acLDL.
[3H] cholesteryl oleate was incorporated into the core of acLDL by exchange of tracer incorporated into unilamellar liposomes as described previously (37
). Briefly, liposomes were prepared by combining phosphatidylcholine (egg yolk lecithin, 80 mg/L in PBS, Sigma, St. Louis, MO) with [1
,2(n)-3H]-cholesteryl oleate [100 µCi (3.7 MBq), Amersham Life Science, Buckinghamshire, UK)]. The mixture was then vortexed and evaporated under argon. Radiolabeled liposomes were produced by addition of PBS (550 µL) to the phosphatidylcholine/[3H]-cholesteryl oleate mixture and vortexing for 10 min. Desalted lipoprotein-deficient plasma (1 mL) and LDL (1 mg LDL protein in 1 mL) were added to liposomes and incubated in a shaking water bath (37°C, 20 h). The density of the mixture was adjusted to 1.24 kg/L overlaid by 1.006 kg/L and ultracentrifuged (417,000 x g, 2 h, 15°C) (38
). The radiolabeled acLDL appeared as a distinct band which was recovered by syringe and passed through a 0.8-µm filter. After centrifugation, 21.8% radioactivity derived from [3H]-cholesteryl oleate was recovered, and 80% of LDL protein was recovered. The radioactive concentration of acLDL was 3.8 x 107 dpm/mg LDL protein.
Cannulation of the jugular vein.
Rats used in the in vivo assay of RCT underwent bilateral cannulation of the jugular vein as described previously (39
). Rats were anesthetized with intraperitoneal injections of sodium pentobarbitone (30 mg/kg body; Nembutal, Boehringer Ingelheim, Artarmon, NSW) and ketamine hydrochloride (50 mg/kg body; Ketamil Injection BP, Troy Laboratories, Smithfield, NSW). Upon full anesthesia, the ventral thoracic and dorsal neck regions were shaved and prepared for surgery by thorough swabbing of exposed skin with 10% iodine. A small incision (10 mm) was made directly above the jugular vein. The vein was exposed by back dissection of the underlying tissue. It was then teased away from surrounding connective tissue and isolated over a metal support. The anterior section of vein was tied off with silk suture to prevent blood flow from the brain. Posterior to the ligature, a 1-mm incision was made in the vein to allow for the insertion of a length of silastic tubing (0.51 mm i.d., 0.94 mm o.d.; Dow Corning Silastic Tubing, Pennant Hills, Australia) filled with 9 g/L saline containing 1 x 105 U/L heparin. The posterior portion of the vein was secured around the cannula with silk suture. The procedure was repeated for the opposite jugular vein. The cannulas were then threaded subcutaneously from the ventral thoracic region to exit through a 5-mm incision in the dorsal neck region. Patency of both cannulas was ensured; then the thoracic incisions were stitched and the cannulas plugged with metal stoppers. Postoperatively, rats were housed individually and allowed to recover for 48 h before use in the kinetic experiment.
Administration of radiolabeled acLDL and blood collection.
Heparinized saline was removed from the left catheter. Labeled acLDL were administered (3.7 x 106 dpm, 200 µL) via the left catheter, which was then flushed with heparinized saline (100 µL). AcLDL were cleared within minutes of injection, mainly by hepatic endothelial cells, and then transferred to hepatocytes (24
). The reappearance of radiolabel into plasma and HDL was followed at timed intervals in blood samples (200 µL) collected from the right catheter (2 and 30 min, 1, 2, 4, 8, 12 and 24 h). Rats were exsanguinated after collection of the last sample. Blood was collected into tubes containing EDTA (1 mmol/L); the liver was excised, blotted on lint-free tissue and stored at -80°C until analysis. Blood was centrifuged (5000 x g, 1 min) and the plasma stored at -80°C. To determine the reappearance of label into plasma, aliquots of plasma were applied to glass fiber discs and allowed to dry. The glass fiber discs were then placed into scintillation vials and 5 mL scintillation fluid was added (toluene, 0.3% 2,5-diphenyloxazole). The radioactivity was determined by liquid scintillation counting as described previously. To follow the reappearance of label into HDL, apo B–containing lipoproteins were precipitated from plasma and the radioactivity determined in an aliquot of the supernatant. The data were plotted as the percentage of injected dose reappearing in plasma and HDL over time.
We previously compared HDL kinetic data obtained by either precipitation or ultracentrafugation techniques (40
). We showed that the profile of radioactivity that appeared in HDL isolated by ultracentrifugation was similar to that obtained by precipitation (40
). Hence in the study we utilized the precipitation technique.
Statistical analysis. Data were analyzed by factorial ANOVA and Scheffe’s test (Statview 4.02, Abacus Concepts, Berkeley, CA). Data are presented as mean ± SEM. Statistical significance was taken at levels of P < 0.05 (two-tailed).
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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). Rats fed the SAT diet had intermediate levels of total cholesterol. Plasma HDL-C concentrations did not differ between rats fed the CIS and TRANS diets, but were 15% lower than their SAT-fed counterparts (Fig. 1)
. The non-HDL-C concentration was 27% lower in rats fed the SAT diet (P < 0.01) and 33% lower in those fed the TRANS diet (P < 0.005) relative to their CIS-fed counterparts. The total cholesterol to HDL-C ratio, a strong predictor of CHD risk in humans (18
), was lower (i.e., protective) in rats fed either the SAT (2.46 ± 0.30, P < 0.005) or TRANS diet (2.60 ± 0.46, P < 0.05) compared with those fed the CIS diet (3.14 ± 0.57).
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The concentration (41
) and linoleic:linolenic acid ratio (20
) of HDL phospholipids have been shown to be positively correlated with the ability of HDL to accept free cholesterol. HDL phospholipids were higher (P < 0.05) in rats fed the SAT diet (1.18 ± 0.10 mmol/L) compared with rats fed either the CIS or TRANS diets, which did not differ (0.96 ± 0.07 and 0.91 ± 0.16 mmol/L, respectively). The ratio of linoleic acid to linolenic acid in HDL phospholipid tended to be higher (P = 0.068) in rats fed the SAT diet (15.3 ± 2.9 mmol/L) compared with those fed the TRANS diet (9.0 ± 4.5 mmol/L), whereas it was intermediate in the CIS group (11.4 ± 2.8 mmol/L). The HDL cholesterol to protein ratio was not affected by diet (0.23 ± 0.03, 0.24 ± 0.02, 0.22 ± 0.02; CIS, SAT and TRANS diet groups, respectively). The HDL phospholipid fatty acid composition reflected that of the diet and indicated that TFA were incorporated into HDL phospholipids at the expense of stearic and palmitic acids. The proportions of HDL phospholipids as saturated, cis- and trans-monounsaturated, and polyunsaturated fatty acids (PUFA) are shown in Table 2
.
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45% of the injected dose remaining after 2 min and 1.3% remaining after 45 min. The rapid clearance of acLDL-associated [3H] from plasma is consistent with that demonstrated by other workers in which <1% remained after 1 h (24
). [3H] reappeared in plasma in steadily increasing amounts until it reached a maximum of 7.1–8.4% of the injected dose after 18 h and then decreased slightly to 6.6–7.5% of the injected dose by 24 h (Fig. 2
). There was an apparent steady state between 12 and 18 h due to influx and efflux of radioactivity.
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To determine the residual hepatic radioactive concentration and the proportions of free and esterified cholesterol, livers were excised from rats used in the kinetic experiment after the collection of the final blood sample. Compared with CIS-fed rats, the radioactive concentration of hepatic tissue (expressed as dpm/g liver) was 13% lower in rats fed the SAT diet (P = 0.077) and 23% lower in rats fed the TRANS diet (P < 0.005). The proportion of labeled cholesterol as cholesteryl ester was highest in rats fed the CIS diet, whereas those fed the SAT and TRANS diets had similar yet much lower proportions of cholesteryl ester in liver (P < 0.0001; Table 3
). These differences are most likely due to the greater specificity of the acyl CoA:cholesterol-O-acyltransferase enzyme for fatty acyl-CoA esters of oleic acid compared with those of palmitic acid or TFA (42
).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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,6
,7
), the results indicate that TFA lower LDL-C with no effect on HDL-C in an animal model devoid of plasma CETP activity. This suggests that dietary TFA have a role in regulating the metabolism of apo B–containing lipoproteins in rats and that the effect may be masked in species possessing CETP activity.
Lower levels of hepatic [3H]-cholesterol were detected in rats fed the TRANS diet compared with those fed the CIS diet. In agreement with our observation, Sugano and colleagues (43
) found lower concentrations of hepatic cholesterol in rats fed cholesterol-free diets containing trans octadecenoic acids compared with those fed diets containing the cis isomer. Rats fed TFA also had greater cholesterol 7-hydroxylase activity and consequently higher rates of fecal excretion of cholesterol. Kinetic studies showed that rats fed TFA had reduced cholesterol mass in the rapidly exchangeable pool, and the authors proposed that this was due to higher rates of assimilation into intestinal epithelial cells and higher rates of excretion into feces. In the presence of dietary cholesterol (0.5 g/100 g) (44
), rats fed TFA had lower plasma total cholesterol concentrations than those fed similar levels of the cis isomer.
The plasma HDL-C concentration is clearly important in protecting against CHD. Recent evidence suggests the dietary fatty acid composition can influence the composition of HDL particles (20
); therefore, it may play a role in determining the capacity of HDL particles to accept cholesterol. Sola and co-workers (20
) fed normolipidemic women diets enriched in either saturated, monounsaturated, (n-6) polyunsaturated or (n-3) PUFA for 7-wk periods. In vitro experiments showed that HDL3 particles isolated after consumption of the monounsaturated fatty acid diet induced the greatest degree of cholesterol efflux from cultured human fibroblasts, followed by the (n-6) polyunsaturated, saturated and (n-3) PUFA diets, respectively. Factors associated with increased capacity of HDL3 to promote cellular cholesterol efflux in vitro were increased fluidity, cholesteryl ester content, phospholipid linoleic to linolenic acid ratio and smaller particle size. In a study by Davidson and colleagues (21
) however, the ability of reconstituted HDL particles to accept cellular cholesterol in vitro was positively associated with the phospholipid acyl chain length and the degree of unsaturation. When investigated in vivo, modifications in HDL phospholipid acyl chain composition resulting from dietary manipulation in African Green monkeys did not affect efflux from mouse L-cell fibroblasts (45
). Further in vivo studies are required to clarify the discrepancies in the effects of dietary modification on cholesterol efflux.
Rats fed diets with varying fatty acid composition displayed diet-induced differences in the composition of HDL particles. TRANS-fed rats had a reduced proportion of saturated fatty acids in HDL phospholipids compared with rats fed either the CIS or SAT diet. TFA were incorporated into HDL phospholipids at the expense of saturated fatty acids, mainly stearic acid, and to a lesser degree, palmitic acid. Also, rats fed the SAT diet had significantly higher concentrations of HDL-phospholipid (P < 0.05) than those fed the CIS or TRANS diets. In light of the diet-induced differences in HDL composition, we conducted an in vivo assay of RCT in a subset of rats to compare the effects of these fatty acids on the capacity of HDL particles to accept cellular free cholesterol. Rats were injected with acetylated LDL containing [3H]-cholesteryl oleate. The labeling of the particle in the core and the lack of CETP activity in the rat ensured minimal transfer of label before tissue uptake. This mode of delivery rapidly loads the reticuloendothelial system (mostly hepatic) with esterified [3H]-cholesterol, which can be hydrolyzed and released to acceptor particles such as HDL in the circulation (24
,40
,46
). Blood was collected at timed intervals to determine the reappearance of radiolabel into plasma and HDL. The proportion of plasma radioactivity associated with HDL particles reached 40% 4 h postinjection. Consistent with the model used in this study, data from a recent report by Alam et al. (47
) showed that most of the cholesterol that appears in plasma after the infusion of reconstituted HDL is derived from the liver and accumulates in HDL in mice lacking CETP. These observations were made under conditions of low dietary cholesterol and may differ under conditions of high cholesterol or variations in the fatty acid composition of the diet.
In accordance with previous studies (24
,40
) the majority of radiolabeled cholesterol injected in the form of acLDL is cleared rapidly from the circulation and reappears in plasma and erythrocytes. Using procedures identical to those described in the present study, we showed previously (40
) that the appearance of radiolabel in plasma reaches a maximal level of 6% of the injected dose compared with 8% in the present study. A key difference between the present study and our previous report is the level of dietary fat, i.e., 35% in the present study compared with low fat nonpurified diets in the former.
Despite differences in HDL composition, the appearance of label in HDL was similar among groups when expressed as a percentage of initial radioactivity or as specific activity (data not shown). These in vivo data suggest that rats fed the TRANS diet have HDL particles with similar capacity for RCT as those fed the diets high in oleic or palmitic acids. Woollett and co-workers (48
) recently investigated the relationship between diet-induced changes in circulating HDL-C concentrations and the rate of RCT in hamsters. They found that the absolute flux of cholesteryl ester to the liver remained constant despite a twofold difference in plasma HDL-C concentrations. The authors suggested that processes occurring within the peripheral cell to regulate the rate of movement of cholesterol from the endoplasmic reticulum to the plasma membrane are the primary determinants of the rate of RCT. In agreement with the work of Woollett and co-workers (48
), the results of the in vivo assay of RCT presented here showed that the reappearance of label into HDL was similar in the groups despite differences in plasma HDL-C concentrations. It has been suggested that differences in plasma HDL-C concentrations are more likely to be the consequence of differential rates of apo A-I production (49
); in the case of TFA-mediated reductions in HDL-C concentrations in humans, they are more likely due to effects on the activity of plasma lipoprotein modeling enzymes such as CETP. Nevertheless, the mechanism by which HDL cholesterol is protective against coronary heart disease remains to be clarified. Alam et al. (47
) showed that despite increases in cholesterol efflux as a result of the administration of reconstituted HDL, cholesterol flux through the multicompartment of the RCT pathway was not increased.
HDL are structurally heterogeneous due to their continual remodeling by numerous factors including transfer proteins such as CETP and phospholipid transfer protein as well as enzymes such as lecithin cholesterol acyltransferase and hepatic lipase (50
,51
). These modifications result in HDL particles with diverse functions. Characteristics of HDL other than lipid composition per se have been shown to affect cholesterol efflux. In Tangier disease, it has been shown that HDL particle size is positively correlated with cholesterol efflux from macrophages (52
). In the present study, the effect of the dietary manipulation on HDL particle size is not known.
In conclusion, compared with oleic acid, rats, which are devoid of plasma CETP activity, respond to dietary TFA by a reduction in lower density lipoproteins without any effect on HDL-C. This is in direct contrast to the effect observed in humans and other species possessing plasma CETP activity. These data suggest a role of TFA in regulating the metabolism of apo B–containing lipoproteins and that the effect may be masked in the presence of CETP activity. Although this phenomenon may involve other intrinsic factors, our data reinforce the important role of CETP activity in determining the distribution of plasma cholesterol in response to dietary TFA in humans.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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3 Abbreviations used: acLDL, acetylated LDL; apo B, apolipoprotein B; CETP, cholesteryl ester transfer protein; CHD, coronary heart disease; CIS diet, oleic acid; FAME, fatty acid methyl esters; HDL-C, HDL cholesterol; Lp(a) lipoprotein (a); LDL-C, LDL cholesterol; PUFA, polyunsaturated fatty acids; RCT, reverse cholesterol transport; SAT diet, palmitic acid; TFA (TRANS diet), trans fatty acids.
Manuscript received 15 October 2001. Initial review completed 20 November 2001. Revision accepted 21 February 2002.
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LITERATURE CITED |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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) SAT diet; (
) CIS diet; (•) TRANS diet. Values are means ± SEM, n = 12. aCIS significantly different from SAT, P < 0.05; bTRANS significantly different from SAT, P < 0.05.