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Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48202
4To whom correspondence should be addressed. E-mail: pkhosla{at}sun.science.wayne.edu.
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ABSTRACT |
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 TOP ABSTRACT MATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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40 g/100 g dietary animal fat with vegetable oil would improve plasma lipids and lipoproteins when diets contained prudent levels of total saturated acid (SFA), monounsaturated acid (MUFA) and PUFA. Using a cross-over design, male Cynomolgus monkeys (n = 10) were fed purified diets containing a mixture of fats. For the diet based on animal fat (AF-diet), 85 g/100 g of the total fat was derived from pork fat, and 40 g/100 g of this was replaced with olive oil for the vegetable oil–based diet (VO-diet). Thus, the fat content of the VO diet comprised 50% pork fat and 35% olive oil. The remaining 15% of the total fat (for both diets) was safflower oil. Both diets provided 30% of total energy (%en) from fat, <10%en SFA and 6–7%en from PUFA. Monkeys were rotated through two 7-wk feeding periods, during which time plasma lipids and lipoproteins were evaluated. Compared with the AF diet, plasma total cholesterol (TC) concentrations tended to be lower (10%) after monkeys consumed the VO diet (3.18 ± 0.83 vs. 3.52 ± 0.93 mmol/L, P = 0.099), and this was due entirely to a significant 12% reduction in HDL cholesterol (1.53 ± 0.41 vs. 1.73 ± 0.47, mmol/L, P = 0.0009). Although plasma lipoprotein compositional analyses revealed no significant differences in either lipoprotein composition or the estimated particle diameters, the measurement of cholesterol ester transfer protein (CETP) using 3H-cholesterol ester–labeled HDL revealed that the lower HDL cholesterol (HDL-C) when monkeys consumed the VO diet was associated with a 31% increase in transfer (P = 0.04). However, despite the changes in HDL-C, the TC/HDL-C ratio did not differ between monkeys after the two diet treatments. Regression analyses of data from these monkeys revealed a significant correlation between the dietary 16:0/18:2 ratio and plasma HDL-C. These data suggest that within the context of currently recommended prudent diets, it may be possible to manipulate HDL-C beneficially. Whether a similar effect would occur in humans warrants investigation.
KEY WORDS: • pork fat • vegetable oil • cynomolgus monkeys • low density lipoprotein • high density lipoprotein
Primary management of hypercholesterolemia calls for diets that restrict saturated fatty acids (SFA) and/or dietary cholesterol. The basis for these recommendations is rooted in classic studies (1,2) that have been supported by several meta-analyses (3–5) showing that SFA increased circulating cholesterol, whereas PUFA lower cholesterol. These recommendations are "quantified" in the latest guidelines from the American Heart Association (AHA) and the National Cholesterol Education Program (NCEP) Adult Treatment Panel III and reflect SFA intakes < 7% of total energy (en%) and dietary cholesterol < 300 mg/d for the general healthy population [<200 mg/d for subjects with established coronary heart disease (CHD) risk factors] (6,7).
Of the individual SFA, myristic acid (14:0) and palmitic acid (16:0) are the main contributors to LDL cholesterol (LDL-C) elevation. Even though 14:0 is the most potent SFA in elevating LDL-C, 16:0 is considered the major contributor to SFA-induced hypercholesterolemia because it is the most abundant SFA in the diet (1–3,5,8). However, beginning in the early 1990s, a series of studies from Hayes’ group (9–15) drew attention to the fact that the putative effect of any fatty acid is dependent on both the metabolic status of the individual as well as the other dietary fatty acids present. Thus, in normocholesterolemic subjects (cebus, rhesus and squirrel monkeys) consuming very low cholesterol–containing or cholesterol-free diets, 16:0 did not affect LDL-C levels; in such situations, the effects of 16:0 were similar to those of oleic acid [18:1] (9–12). Only when LDL receptors were suppressed by cholesterol feeding did 16:0 have a hypercholesterolemic effect compared with 18:1 (12). In a meta-analysis of data from cebus monkeys (13), it was shown that in normocholesterolemic monkeys consuming low cholesterol diets (reflecting unimpaired LDL receptor activity), total cholesterol (TC) and LDL-C were dependent solely on the dietary content of 14:0 and linoleic acid [18:2]. Furthermore, above a "threshold" level of 18:2 of 5–6%en, other fatty acids appeared essentially equivalent. Similar effects were noted in gerbils and hamsters (16,17). A subset analysis of published human data (1) suggested that a similar situation might exist in humans, especially when dietary fat and cholesterol intake is moderate (12). This has since been confirmed in several human studies (14,15,18,19) that found dietary 16:0 to be equivalent to 18:1. A meta-analysis of >30 human studies (encompassing 130 diets) yielded similar results, adding further support to Hayes’ argument that 16:0 is "conditionally hypercholesterolemic" or "conditionally neutral" (20).
As a continuing test of the above ideas, we recently reported (21,22) the effects of exchanging 16:0 for 18:0 (universally regarded as neutral) on plasma lipoprotein metabolism, using cholesterol-free diets with comparable total SFA, monounsaturated fatty acids (MUFA) and PUFA contents. By satisfying the conditions outlined in Hayes’ threshold hypothesis, we were able to directly compare a 5%en exchange between 16:0 and 18:0 and found no difference in plasma lipids or lipoprotein metabolism in hamsters (21) or cynomolgus monkeys (22) when diets contained levels of 18:2 that were above threshold.
In the current study, we have extended the above observations by evaluating the effects on plasma lipids and lipoproteins of replacing 40 g/100 g animal fat with an equivalent amount of vegetable oil, within the same dietary settings employed earlier (22,23). The cynomolgus monkey was again utilized because it is an invaluable model for evaluating the effects of individual fatty acids on plasma lipids. Our data showed that within the framework of the threshold hypothesis, in addition to maintaining low levels of LDL-C, it may also be possible to increase HDL cholesterol (HDL-C).
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MATERIALS AND METHODS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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Male cynomolgus monkeys (n = 10) (Macaca fasicularis), born between 1990 and 1993, were used for the current study. All monkeys were fed purified diets, whose composition is detailed in Table 1. The purified diets were pelleted by Dyets (Bethlehem, PA). The two test diets were formulated according to current dietary guidelines for total fat and SFA (30% en total fat, 10%en SFA). No exogenous cholesterol was added to the diets. For the animal fat–based diet (AF-diet), 85% of the total fat was derived from pork fat, whereas for the vegetable oil–based diet (VO-diet), 40% of the pork fat was replaced with olive oil. Thus the VO-diet comprised 50% pork fat and 35% olive oil. The remaining 15% of the fat (for both diets) was safflower oil (18:2 rich). The resulting fatty acid composition is shown in Table 2. The rendered pork fat used in the current study as well as its fatty acid and cholesterol content were described earlier (23). Briefly, it consisted of adipose tissue from butcher-weight hogs slaughtered in Illinois and Iowa. The rendered pork fat was shipped to Dyets for diet preparation. The diet manufacturer provided all other ingredients. Diets (prepared in a single batch for the entire duration of the study) were stored at -20°C and 5-kg batches removed as needed for daily feeding to the monkeys. These batches were kept refrigerated.
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Monkeys were fed a fixed amount of food daily (110–220 g/d, divided equally between a morning and an afternoon feed), designed to maintain constant body weights throughout the study period. All procedures and protocols were in accordance with, and ratified by, the University’s Health Physics Department (radioactivity compliance) and the Animal Investigation Committee. All procedures used were minor modifications to a detailed protocol recently reported for these same monkeys (22,23).
Plasma lipid determinations.
After overnight food deprivation (14–16 h), monkeys were anesthetized with an intramuscular injection of Ketamine HCl (Vetalar, Parke-Davis, Morris Plains, NJ, 10 mg/100 µL) at a dose of 4–9 mg/kg body. Blood was obtained from the saphenous or femoral vein and placed into EDTA-wetted tubes kept on ice. Plasma was isolated by centrifugation at 1000 x g, 20 min, 4°C. TC, triglyceride (TG) and HDL-C concentrations were determined as detailed previously (22,23). The difference between TC and HDL-C represented VLDL + LDL cholesterol.
Plasma lipoprotein isolation and characterization.
Sodium azide, gentamycin sulfate, benzamidine and EDTA (24,25) were added to plasma samples before lipoprotein isolation.
At wk 7, lipoproteins were separated from individual monkey plasma using a 5-step discontinuous salt gradient by density gradient ultracentrifugation as described by Goulinet and Chapman (26) and detailed previously (22,23). From a plot of fraction number, density and cholesterol content, two major peaks and one minor peak were discernible. On the basis of this cholesterol distribution, lipoprotein fractions were pooled to yield fraction 1, designated VLDL (d < 1.019 kg/L), fraction 2, designated LDL (1.019 < d <1.063 kg/L), and fraction 3, designated HDL (1.063 < d <1.21 kg/L).
Lipoprotein lipid compositions were determined enzymatically as described previously (22,23). Lipoprotein protein concentrations were determined using the Markwell modification (27) of the Lowry procedure (28). Particle diameters of each lipoprotein class were estimated from the core-to-surface volume ratios (29).
Plasma cholesterol ester transfer protein (CETP) activity.
This was examined using the modifications of Khosla et al. (30). CETP activity in duplicate10-µL aliquots of monkey plasma was determined after incubations with 3H-cholesterol ester (CE)-labeled HDL3 and LDL. Radioactivity transferred from 3H-HDL3 to LDL (measured in the supernatant after precipitation with heparin/MnCl2+) was used to calculate CETP activity (expressed as the percentage of radioactivity transferred from 3H-HDL3 to LDL per 16 h of incubation). CETP measurements (on plasma samples from monkeys fed the two diets) were conducted using aliquots of frozen plasma (-70°C) after 4 wk of dietary treatment.
Statistical analyses.
All statistical analyses were performed using a Power Macintosh 6100 computer (Apple Systems, Cupertino, CA) with the StatView 512+ (Brain Power, Calabasas, CA) statistical package. Data were analyzed by repeated-measures ANOVA with differences considered significant at P < 0.05. Results are presented as means ± SD.
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RESULTS |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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Plasma total cholesterol concentrations (means of the 6- and 7-wk samples) tended to be lower (10%) after monkeys consumed the VO-based diet (P = 0.099, Table 3), which was due entirely to a significant 12% reduction in HDL-C concentration. As a consequence, the TC/HDL-C ratio did not differ between the AF- or VO-feeding periods. Of the total cholesterol, 48% was in the HDL fraction, whereas the remainder was associated with the apo B–containing lipoproteins. However, the diets did not affect non-HDL-C. Plasma TG concentrations were significantly decreased by 10% after monkeys consumed the VO-diet (Table 3). Isolated lipoprotein fractions did not differ due to diet treatment in the percentage composition of any of the constituents (Table 4), or in the estimated diameters of lipoprotein particle (Table 5).
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DISCUSSION |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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6–7%en, for the AF and VO diets) was above or close to the threshold level for 18:2 (5–6%en) proposed (13,17). Finally, 14:0, the most potent cholesterol-elevating fatty acid, was present in insufficient amounts (0.3%en) to affect LDL levels. Even though the content of 16:0 was 20% higher in the AF diet, based on Hayes’ hypothesis, this would have been predicted to make no contribution to plasma LDL cholesterol. Thus, the current dietary manipulation produced essentially similar effects on the latter. On the basis of the above discussion, it follows that in diets with a moderate fat and cholesterol load, minimum amounts of 14:0 and at least 5–6%en from 18:2, the remaining fatty acids (mainly 16:0, 18:0 and 18:1) should have very little effect on LDL-C, especially in situations of normal LDL receptor activity. The NCEP Step 1 and the current therapeutic lifestyle change diet essentially satisfy most of the above conditions. Thus it can be predicted that within the above dietary setting any fat source is acceptable. The current data, coupled with data from our two previous studies in these same monkeys (22,23), further support the above tenets and are consistent with the following:
1) Plasma LDL-C (non-HDL-C because cynomolgus monkeys have low circulating VLDL-C) was 1 mmol/L when monkeys were fed a low fat, low cholesterol, nonpurified diet (23). Because LDL receptors function maximally at plasma LDL-C concentrations of 0.6 mmol/L (32), our value of LDL-C for the low fat, low cholesterol, nonpurified diet is close to the theoretical minimum, and is similar to what is seen in most animal species fed similar diets.
2) Feeding a high fat (38%en), high cholesterol (180 mg/4200 kJ) diet elevated LDL-C to 3.8 mmol/L (23). The affinity of the LDL particle for its receptor is relatively uniform in different species with a Kd of 2.3 mmol/L (33). Thus, with LDL-C of 2.8 mmol/L, the rate of LDL-C removal (or uptake) via LDL receptors would be expected to be 50% of the maximum that can be achieved (i.e., the rate when LDL-C is 0.6 mmol/L). LDL-C generally changes little until LDL receptors are suppressed >50% (34). Thus, the level of LDL-C in these monkeys after consumption of the high fat, high cholesterol diet is consistent with a >50% suppression of the LDL receptors, resulting in a steep and sharp increase in LDL-C. Although the latter is due almost entirely to the dietary cholesterol in cynomolgus monkeys, this level of LDL-C is consistent with a >50% suppression of the LDL-C receptors.
3) When Step 1-type diets were fed (30%en fat, <100 mg cholesterol/4200 kJ, with 
10%en SFA and 10%en PUFA), LDL-C levels were 1.9 mmol/L, consistent with 0–50% LDL receptor suppression. (In humans these levels would be considered desirable.) Thus, monkeys readily "sustained" a 50% loss of LDL-receptor activity (when LDL-C approached 2.3 mmol/L) and maintained "desirable" levels of LDL-C. In human populations characterized by low CHD risk, LDL-C is frequently <2.3 mmol/L (34).
4) Regardless of the "saturated" fat sources used to formulate the "Step 1 type diets" (palm oil, cocoa butter, pork fat, chicken fat), as long as the dietary criteria were satisfied (i.e., 30%en fat, <100 mg cholesterol/4200 kJ, with 10%en SFA and 10%en PUFA), LDL-C remained 1.8 mmol/L. Thus, the choice of "saturated fat" was not important because LDL-C was not affected. Within this dietary framework, even the presence of 18:0 (up to 50% of total SFA) did not confer any advantage on plasma lipid levels (22). Cynomolgus monkeys have frequently been used for atherosclerotic endpoints and dietary fat x cholesterol interaction studies. Our data provide further evidence of the appropriateness and validity in using this model for evaluating dietary fatty acid–induced lipid responses per se, even in the absence of dietary cholesterol.
An unexpected and interesting finding from the current study was the degree of difference in HDL-C levels. Despite the significant difference in HDL-C between the monkeys when they consumed the two diets, we did not detect any differences in lipoprotein composition. Inspection of the fatty acid composition in Table 2 reveals that compared with the VO-diet, the AF-diet had a 32% higher SFA content and a 13% lower PUFA content, resulting in an almost 35% lower polyunsaturated/saturated (P/S) ratio. The differential in SFA content was due principally to differences in 16:0 and 18:0 (20 and 32% higher in the AF-diet, respectively). These differences, on face value, do not appear to be dramatic enough to explain the 14% higher HDL-C when the AF-diet was fed. [Application of human regression equations (5) predicted HDL-C changes on the order of <0.026 mmol/L.] Accordingly, we analyzed all of the diets fed to these monkeys in this study and previously (22,23). Using criteria detailed elsewhere (13,16), regression analyses revealed that for HDL-C, the strongest predictor was the ratio of 16:0/18:2 (r = 0.87, P < 0.01). A similar relationship was noted in an analysis of published data (9,11,12,30) from cebus monkeys employing comparable dietary settings (r = 0.79, P < 0.05, Fig. 3). This finding of an association between dietary 16:0/18:2 with plasma HDL-C was first suggested indirectly by Sundram et al. (15), when they proposed that a minimum amount of dietary SFA may be required to have beneficial effects on HDL-C. On the basis of our above regression results, we prepared two additional diets (16:0/18:2 ratios of 1.25 and 2.13) and fed them to monkeys for 6 wk in a cross-over design. Our regression equation predicted HDL-C concentrations of 1.68 and 1.84 mmol/L, respectively, which were close to the actual values of 1.76 ± 0.31 vs 1.94 ± 0.34 mmol/L, respectively (Gupta and Khosla, unpublished observations).
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Fatty acid classes have been shown to affect CETP activity. Thus trans fatty acids (specifically trans monounsaturates) lower HDL-C in part by increasing CETP (31,35,36). These observations, coupled with the fact that we had frozen plasma samples from the current study, prompted us to evaluate CETP. An initial analysis of plasma collected after 4 wk of treatment revealed both a strong inverse correlation between plasma HDL-C and CETP and a significantly higher CETP activity in samples from monkeys fed the VO-diet. Our observation concerning the negative correlation between plasma HDL-C level and CETP activity agrees with studies in various animals including rats, dogs, hamsters, rabbits and monkeys (37), as well as studies in humans (38,39). Dietary influences on CETP have been demonstrated in many studies. It has been reported that dietary cholesterol increases CETP levels in rabbits (40), hamsters (41), nonhuman primates (42,43) and humans (44). Because our diets were essentially cholesterol free, the effects were most likely due to manipulation of the dietary fatty acids. In an in vitro study using nonesterified fatty acids (45), it was noted that the percent transfer of 3H-CE to LDL with SFA was lower (35%) than with PUFA (50%), consistent with our observation that monkeys fed the VO-diet, with a higher P/S ratio (0.98), had higher CETP activity than those fed the AF-diet with its lower P/S ratio (0.64). Although several studies have examined alterations of CETP levels induced by fatty acid composition, there is no general agreement on the effects of individual fatty acids. For instance, no differences were found in activity (43,46,47) or plasma concentration (43,47) of CETP due to diets high in SFA, MUFA or PUFA. Hirano et al. (48) suggested that as fatty acid unsaturation and carbon-chain length increase, CETP mass and mRNA level decrease. This discordance between results may relate to the broad classification of fatty acids (i.e., SFA, MUFA and PUFA), which masked the different effects of individual fatty acids. Thus, both the combination and the ratio of fatty acids should be considered in future studies investigating dietary modulation of CETP levels.
In several previous studies, increased CETP and decreased HDL-C were frequently associated with elevations in circulating LDL-C, whereas no such change was noted in the current study. This is probably due to the fact that in our monkeys, LDL receptors were maximally expressed as a consequence of the lack of dietary cholesterol and the presence of adequate amounts of 18:2. Thus, any CE transferred from HDL-C to LDL-C would not be discernible because the LDL would have been rapidly cleared from the plasma (30). In contrast, when dietary cholesterol is present, a certain degree of LDL receptor downregulation would be expected. Accordingly, after CETP-mediated CE transfer from HDL to LDL, the LDL particle would circulate in the plasma much longer due to impaired receptor-mediated clearance, resulting in an elevation in LDL-C (43). In pilot studies in transgenic mice (expressing both human CETP and apoB100), the consumption of diets with extreme ratios of 16:0/18:2 also revealed significant elevations in HDL-C with the high ratio, with essentially little effect on non-HDL-C (Yamada et al., unpublished observations).
On the basis of recent studies, it is possible that the ATP-binding cassette transporter, ABCA1, may have influenced HDL-C. Recent reports have noted that unsaturated fatty acids, compared with SFA, downregulate ABCA1 in Hep G2 cells (49) and inhibit cholesterol efflux from macrophages (50). Overexpression of ABCA1 in mice resulted in elevated HDL-C (51). Because ABCA1 levels are upregulated in the liver after consumption of an atherogenic diet (52), rich in SFA + cholesterol (very little PUFA), it seems plausible that progressive addition of dietary 18:2 to above-threshold levels may lead to ABCA1 downregulation and a subsequent decrease in HDL-C.
Hepatic mRNA levels of SR-B1 were 50% higher in hamsters fed safflower oil than the levels observed in those fed coconut oil (53). The mRNA changes were paralleled by changes in SR-B1 protein levels with the latter inversely related to HDL-C. In hamsters, HDL-C was negatively correlated with hepatic SR-B1 mass, which in turn was negatively correlated with dietary 14:0 content (54). When rats were fed purified diets supplemented with tripalmitin and triolein, hepatic SR-B1 protein was increased by triolein feeding (55). Thus, it will be important to quantitate the effects of individual fatty acids on SR-B1 expression, within the context of currently recommended dietary practices.
In summary, our data provide further support for the validity of using cynomolgus monkeys to investigate dietary fatty acid–induced effects on lipoprotein metabolism, even in the absence of dietary cholesterol. Furthermore, our data suggest that in Cynomolgus and cebus monkeys, the dietary ratio of 16:0/18:2 may modulate circulating HDL-C, in part by altering CETP. Whether the same relationship holds for humans following current dietary recommendations warrants investigation.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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2 Supported in part by a grant from the National Pork Producers Council.
3 Present address: Oxford Biomedical Research, Rochester Hills, MI 48371.
5 Abbreviations used: ABCA1, ATP-binding cassette transporter A1; AF, animal fat; AHA, American Heart Association; CE, cholesterol ester; CETP, cholesterol ester transfer protein; CHD, coronary heart disease; en%, % of total energy; HDL-C, HDL cholesterol; LDL-C, LDL cholesterol; MUFA, monounsaturated fatty acid; NCEP, National Cholesterol Education Program; P/S, polyunsaturated/saturated ratio; SFA, saturated fatty acid; SR-B1, scavenger receptor-B1; TC, total cholesterol: TG, triglyceride; VO, vegetable oil
Manuscript received 22 January 2003. Initial review completed 25 March 2003. Revision accepted 8 May 2003.
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LITERATURE CITED |
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TOPABSTRACTMATERIALS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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1. Hegsted, D. M., McGandy, R. B., Myers, M. L. & Stare, F. J. (1965) Qualitative effects of dietary fat on serum cholesterol in man. Am. J. Clin. Nutr. 17:281-295.[Medline]
2. Keys, A., Anderson, J. T. & Grande, F. (1965) Serum cholesterol response to changes in diet. IV. particular saturated fatty acids in the diet. Metabolism 14:776-787.
3. Mensink, R. P. & Katan, M. B. (1992) Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Arterioscler. Thromb. 12:911-919.
4. Hegsted, D. M., Ausman, L. M., Johnson, J. A. & Dallal, G. E. (1993) Dietary fats and serum lipids: an evaluation of the experimental data. Am. J. Clin. Nutr. 57:875-883.
5. Yu, S., Derr, J., Etherton, T. D. & Kris-Etherton, P. M. (1995) Plasma cholesterol-predictive equations demonstrate that stearic acid is neutral and monounsaturated fatty acids are hypocholesterolemic. Am. J. Clin. Nutr. 61:1129-1139.
6. American Heart Association (2000) Dietary guidelines: revision 2000: a statement for healthcare professionals from the Nutrition Committee of the American Heart Association. Circulation 102:2284-2299.
7. Adult Treatment Panel III/NCEP 2001 http://www.nhlbi.nih.gov/guidelines/cholesterol/profmats.htm.
8. Zock, P. L., de Vries, J.H.M. & Katan, M. B. (1994) Impact of myristic versus palmitic acid on serum lipid and lipoprotein levels in healthy women and men. Arterioscler. Thromb. 14:567-575.
9. Hayes, K. C., Pronczuk, A., Lindsey, S. & Diersen-Schade, D. (1991) Dietary saturated fatty acids (12:0, 14:0, 16:0) differ in their impact on plasma cholesterol and lipoproteins in nonhuman primates. Am. J. Clin. Nutr. 53:491-498.
10. Pronczuk, A., Patton, G. M., Stephan, Z. & Hayes, K. C. (1991) Species variation in the atherogenic profile of monkeys: relationship between dietary fats, lipoproteins and platelet aggregation. Lipids 26:213-222.[Medline]
11. Khosla, P. & Hayes, K. C. (1992) Comparison between dietary saturated (16:0), monounsaturated (18:1) and polyunsaturated (18:2) fatty acids on plasma lipoprotein metabolism in cebus and rhesus monkeys fed cholesterol-free diets. Am. J. Clin. Nutr. 55:51-62.
12. Khosla, P. & Hayes, K. C. (1993) Dietary palmitic acid raises plasma LDL cholesterol relative to oleic acid only at a high intake of cholesterol. Biochim. Biophys. Acta 1210:13-22.[Medline]
13. Hayes, K. C. & Khosla, P. (1992) Dietary fatty acid thresholds and cholesterolemia. FASEB J. 6:2600-2607.[Abstract]
14. Ng, T.K.W., Hayes, K. C., de Witt, G. F., Jegathesan, M., Satgunasingham, N., Ong, A.S.H. & Tan, D. T. (1992) Dietary palmitic and oleic acids exert similar effects on serum cholesterol and lipoprotein profiles in normocholesterolemic men and women. J. Am. Coll. Nutr. 11:383-390.[Abstract]
15. Sundram, K., Hayes, K. C. & Siru, O. H. (1995) Both dietary 18:2 and 16:0 may be required to improve the serum LDL/HDL ratio in normocholesterolemic men. J. Nutr. Biochem. 6:179-187.
16. Pronczuk, A., Khosla, P. & Hayes, K. C. (1994) Dietary myristic, palmitic, and linoleic acids modulate cholesterolemia in gerbils. FASEB J. 8:1191-1200.[Abstract]
17. Hayes, K. C., Pronczuk, A. & Khosla, P. (1995) A rationale for plasma cholesterol modulation by dietary fatty acids: modeling the human response in animals. J. Nutr. Biochem. 6:188-194.
18. Choudhury, N., Tan, L. & Truswell, A. S. (1995) Comparison of plamolein and olive oil: effects on plasma lipids and vitamin E in young adults. Am. J. Clin. Nutr. 61:1043-1051.
19. Sundram, K., Ismail, A., Hayes, K. C., Pathmanathan, R. & Jeylamar, R. (1997) Trans (elaidic) fatty acids adversely impact lipoprotein profile relative to specific saturated fatty acids in humans. J. Nutr. 127:514S-520S.
20. Khosla, P. & Sundram, K. (1996) Effects of dietary fatty acid composition on plasma cholesterol Prog. Lipid Res. 35:93-132.
21. Ramamoorthy, L., Gupta, S. V. & Khosla, P. (2000) Effects of exchanging 4%en between dietary stearic and palmitic acid on hamster plasma lipoprotein metabolism Int. J. Food Sci. Nutr. 51:53-61.
22. Gupta, S. V. & Khosla, P. (2001) Palmitic and stearic acid similarly affect plasma lipoprotein metabolism in cynomolgus monkeys fed diets with adequate levels of linoleic acid. J. Nutr. 131:2115-2120.
23. Gupta, S. V. & Khosla, P. (2000) Pork fat and chicken similarly affect plasma lipoprotein metabolism in cynomolgus monkeys fed diets with adequate levels of linoleic acid. J. Nutr. 130:1217-1224.
24. Edelstein, C. & Scanu, A. M. (1986) Precautionary measures for collecting blood destined for lipoprotein isolation. Methods Enzymol. 128:151-155.[Medline]
25. Schumaker, V. N. & Puppione, D. L. (1986) Sequential flotation ultracentrifugation. Methods Enzymol. 128:155-170.[Medline]
26. Goulinet, S. & Chapman, M. J. (1993) Plasma lipoproteins in golden Syrian hamster (Mesocricetus auratus): heterogeneity of apoB- and apoA1-containing particles. J. Lipid Res. 34:943-959.[Abstract]
27. Markwell, M.A.K., Haas, S. M., Bieber, L. L. & Tolbert, N. E. (1978) A modification of the Lowry procedure to simplify protein determination in membrane and lipoprotein samples. Anal. Biochem. 87:206-210.[Medline]
28. Lowry, O. H., Rosebrough, N. J., Farr, A. L. & Randall, R. J. (1951) Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:267-275.
29. Van Heek, M. & Zilversmit, D. B. (1991) Mechanisms of hypertriglyceredemia in the coconut oil/cholesterol-fed rabbit. Arteriosclerosis 11:918-927.
30. Khosla, P., Hajri, T., Pronczuk, A. & Hayes, K. C. (1997) Replacing dietary palmitic acid with elaidic acid (t-C18:1
9) depresses HDL and increases CETP activity in cebus monkeys. J. Nutr. 127:531S-536S.
31. Hayes, K. C. (1995) Saturated fats and blood lipids: new slant on an old story. Can J. Cardiol. 11:39G-46G.
32. Brown, M. S. & Goldstein, J. L. (1986) A receptor-mediated pathway or cholesterol homeostasis. Science (Washington, DC) 232:34-47.
33. Dietschy, J. M., Turley, S. D. & Spady, D. K. (1993) Role of liver in maintenance of cholesterol and low density lipoprotein homeostasis in different animal species, including humans. J. Lipid Res. 34:1637-1659.[Medline]
34. Cerqueira, M. T., Fry, M. M. & Connor, W. E (1979) The food and nutrient intakes of the Tarahumara Indians of Mexico. Am. J. Clin. Nutr. 32:905-915.
35. Abbey, M. & Nestel, P. J. (1994) Plasma cholesteryl ester transfer protein activity is increased when trans-elaidic acid is substituted for cis-oleic acid in the diet. Atherosclerosis 106:99-107.[Medline]
36. Van Tol, A., Zock, P. L., van Gent, T., Scheek, L. M. & Katan, M. B. (1995) Dietary trans fatty acids increase serum cholesteryl ester transfer protein activity in man. Atherosclerosis 115:129-134.[Medline]
37. Tsutsumi, K., Hagi, A. & Inoue, Y. (2001) The relationship between plasma high density lipoprotein cholesterol levels and cholesteryl ester transfer protein activity in six species of healthy experimental animals. Biol. Pharm. Bull. 24:579-581.[Medline]
38. Yamashita, S., Maruyama, T., Hirano, K., Sakai, N., Nakajima, N. & Matuzawa, Y. (2000) Molecular mechanisms, lipoprotein abnormalities and atherogenicity of hyperalpha-lipoproteinemia. Atherosclerosis 152:271-285.[Medline]
39. De Grooth, G. J., Kuivenhoven, J. A., Stalenhoef, A.F.H., De Graaf, J., Zwinderman, A. H., Posma, J. L., Van Tol, A. & Kastelein, J.J.P. (2002) Efficacy and safety of a novel cholesteryl ester transfer protein inhibitor, JTT-705, in humans a randomized phase II dose-response study. Circulation 105:159-2165.
40. Sugano, M., Makino, N., Swada, S., Otsuka, S., Watanabe, M., Okamoto, H., Kamada, M. & Mizushima, A. (1997) Effect of antisense oligonucleotides against cholesteryl ester transfer protein on the development of atherosclerosis in cholesterol-fed rabbits. J. Biol. Chem. 273:5033-5036.
41. Kurushima, H., Hayashi, K., Toyota, Y., Kambe, M. & Kajiyama, G. (1995) Comparison of hypocholesterolemic effects induced by dietary linoleic acid and oleic acid in hamsters. Atherosclerosis 114:213-221.[Medline]
42. Kushwah, R. S., Reardon, C. A., Lewis, D. S., Qi, Y., Rice, K. S., Getz, G. S., Carey, K. D. & McGill, H. C., Jr. (1994) Effect of dietary lipids on plasma activity and hepatic mRNA levels of cholesteryl ester transfer protein in high- and low-responding baboons. Metabolism 43:1006-1012.[Medline]
43. Fusegawa, Y., Kelley, K. L., Sawyer, J. K., Shah, R. N. & Rudel, L. L. (2001) Influence of dietary fatty acid composition on the relation ship between CETP activity and plasma lipoproteins in monkeys. J. Lipid Res. 42:1849-1857.
44. Herron, K. L., Vega-Lopez, S., Conde, K., Ramjiganesh, T., Roy, S., Shachter, N. S. & Fernandez, M. L. (2002) Pre-menopausal women, classified as hypo- or hyper-responders, do not alter their LDL/HDL ratio following a high dietary cholesterol challenge. J. Am. Coll. Nutr. 21:250-258.
45. Lagrost, L. & Barter, P. J. (1991) Effects of various non-esterified fatty acids on the transfer of cholesteryl esters from HDL to LDL induced by the cholesteryl ester transfer protein. Biochim Biophys. Acta 1085:209-216.[Medline]
46. Terpstra, A.H.M., van den Berg, P., Jansen, A., Beynen, A. C. & van Tol, A. (2000) Decreasing dietary fat saturation lowers HDL-cholesterol and increases hepatic HDL binding in hamsters. Br. J. Nutr. 83:151-159.[Medline]
47. Lottenberg, A.M.P., Nunes, V. S., Lottenberg, S. A., Shimabukuro, A. F. M., Carrilho, A.J.F., Malagutti, S., Nakandakare, E. R., McPherson, R. & Quintao, E.C.R. (1996) Plasma cholesterol ester synthesis, cholesteryl ester transfer protein concentration and activity in hypercholesterolemic women: effects of the degree of saturation of dietary fatty acids in the fasting and postprandial states. Atherosclerosis 126:265-275.[Medline]
48. Hirano, R., Igarashi, O., Kondo, K., Itakura, H. & Matsumoto, A. (2001) Regulation by long-chain fatty acids of the expression of cholesterol ester transfer protein in HepG2 cells. Lipids 36:401-406.[Medline]
49. Uehara, Y., Engel, T., Li, Z., Goepfert, C., Rust, S., Zhou, X., Langer, C., Schachtrup, C., Wiekowski, J., Lorkowski, S., Assmann, G. & von Eckardstein, A. (2002) Polyunsaturated fatty acids and acetoacetate downregulate the expression of the ATP-binding cassette transporter A1. Diabetes 51:2922-2928.
50. Wang, Y. & Oram, J. F. (2002) Unsaturated fatty acids inhibit cholesterol efflux from macrophages by increasing degradation of ATP-binding cassette transporter A1. J. Biol. Chem. 277:5692-5697.
51. Singaraja, R. R., Bocher, V., James, E. R., Clee, S. M., Zhang, L.-H., Leavitt, B. R., Tan, B., Brooks-Wilson, A., Kwok, A., Bissada, N., Yang, Y.-Z., Liu, G., Tafuri, S. R., Fieve, C., Wellington, C. L., Staels, B. & Hayden, M. R. (2001) Human ABCA1 BAC transgenic mice show increased high density lipoprotein cholesterol and apoA1-dependent efflux stimulated by an internal promoter containing liver X receptor response elements in Intron 1. J. Biol. Chem. 276:33969-33979.
52. Wellington, C. L., Walker, E.K.Y., Suarez, A., Kwok, A., Bissada, N., Singaraja, R., Yang, Y.-Z., Zhang, L.-H., James, E., Wilsom, J. E., Francone, O., McManus, B. M. & Hayden, M. R. (2002) ABCA1 mRNA and protein distribution patterns predict multiple different roles and levels of regulation. Lab. Investig. 82:273-283.[Medline]
53. Spady, D. K., Kearney, D. M. & Hobbs, H. H. (1999) Polyunsaturated fatty acids up-regulate hepatic scavenger receptor expression and HDL cholesteryl ester uptake in the hamster. J Lipid Res. 40:1384-1394.
54. Loison, C., Mendy, F., Serougne, C. & Lutton, C. (2002) Dietary myrsitic acid modifies the HDL-cholesterol concentration and liver scavenger receptor BI expression in the hamster. Br. J. Nutr. 87:199-210.[Medline]
55. Hatahet, W., Cole, L., Kudchodkar, B. J. & Fungwe, T. V. (2003) Dietary fats differentially modulate the expression of lecithin:cholesterol acyltransferase, apoprotein A1 and scavenger receptor B1 in rats. J. Nutr. 133:689-694.
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