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Hypercholesterolemia represents a significant risk for cardiovascular disease (CVD). While diet intervention remains the initial choice for the prevention and treatment of CVD, the nature of the dietary modification remains controversial. For example, reducing calories from total fat, without decreasing saturated fat intake results in insignificant changes in low density lipoprotein cholesterol (LDL-C). Similarly, diet interventions that focus solely on lowering dietary cholesterol and saturated fat intake not only decrease LDL-C, but also high density lipoprotein cholesterol (HDL-C) and therefore may not improve the lipoprotein profile. This brief review summarizes dietary interventions that lower LDL-C without affecting HDL-C levels. These interventions include soy protein, soluble fiber, soy lecithin and plant sterols. This review also includes some of the reported dietary interventions, such as polyphenols, isoflavones, folic acid and vitamins B6 and B12, which reduce the risk of CVD without changes in lipoprotein cholesterol.

Objective: Our laboratory has previously reported that the hypolipidemic effect of rice bran oil (RBO) is not entirely explained by its fatty acid composition. Although RBO has up to three times more serum cholesterol-raising saturated fatty acids (SATS) than some unsaturated vegetable oils, we hypothesized that its greater content of the unsaponifiables would compensate for its high SATS and yield comparable cholesterol-lowering properties to other vegetable oils with less SATS., Methods: To study the comparative effects of different unsaturated vegetable oils on serum lipoprotein levels, nine cynomologus monkeys (Macaca fascicularis) were fed diets, for four weeks, in a Latin square design, containing rice bran, canola or corn oils (as 20% of energy) in a basal mixture of other fats to yield a final dietary fat concentration of 30% of energy. All animals were fed a baseline diet containing 36% of energy as fat with 15% SATS, 15% monounsaturated fatty acids (MONOS) and 6% polyunsaturated fatty acids (POLYS)., Results: Despite the lower SATS and higher MONOS content of canola oil and the higher POLYS content of corn oil, RBO produced similar reductions in serum total cholesterol (TC) (-25%) and low density lipoprotein cholesterol (LDL-C) (-30%). In addition, as compared to the baseline diet, the reduction in serum TC and LDL-C cholesterol with RBO was not accompanied by reductions in high density lipoprotein cholesterol (HDL-C) which occurred with the other two dietary oils. Using predictive equations developed from data gathered from several studies with non-human primates, we noted that the observed serum TC and LDL-C lowering capabilities of the RBO diet were in excess of those predicted based on the fatty acid composition of RBO., Conclusions: These studies suggest that non-fatty acid components (unsaponifiables) of RBO can contribute significantly to its cholesterol-lowering capability.

Objective: To evaluate the effectiveness of a training program for physician-delivered nutrition counseling, alone and in combination with an office-support program, on dietary fat intake, weight, and blood low-density lipoprotein cholesterol levels in patients with hyperlipidemia., Participants and Methods: Forty-five primary care internists at the Fallon Community Health Plan, a central Massachusetts health maintenance organization, were randomized by site into 3 groups: (1) usual care; (2) physician nutrition counseling training; and (3) physician nutrition counseling training plus an office-support program. Eleven hundred sixty-two of their patients with blood total cholesterol levels in the highest 25th percentile, having previously scheduled physician visits, were recruited. Physicians in groups 2 and 3 attended a 3-hour training program on the use of brief patient-centered interactive counseling and the use of an office-support program that included in-office prompts, algorithms, and simple dietary assessment tools. Primary outcome measures included change at 1-year of follow-up in percentage of energy intake from saturated fat; weight; and blood low-density lipoprotein cholesterol levels., Results: Improvement was seen in all 3 primary outcome measures, but was limited to patients in group 3. Compared with group 1, patients in group 3 had average reductions of 1.1 percentage points in percent of energy from saturated fat (a 10.3% decrease) (P = .01); a reduction in weight of 2.3 kg (P<.001); and a decrease of 0.10 mmol/L (3.8 mg/dL) in low-density lipoprotein cholesterol level (P = .10). Average time for the initial counseling intervention in group 3 was 8.2 minutes, 5.5 minutes more than in the control group., Conclusion: Brief supported physician nutrition counseling can produce beneficial changes in diet, weight, and blood lipids.

Although comparative studies of the cholesterolemic properties of trans fatty acids relative to cis-unsaturates and saturates have been conducted in humans and animals, there is no recent information relating these lipid responses to susceptibility to atherosclerosis. Therefore, hamsters were fed diets containing equivalent amounts of cholesterol (0.12% wt/wt) and test fats (20% wt/wt) for 8 weeks. Each test fat contained between 50-52% of the-total triacylglycerols as a single fatty acid, i.e., 8:0, 14:0, 18:0, cis-18:1, or trans-18:1 while the balance consisted of 16:0, cis-18:1 and 18:2 that were the same for all groups. Plasma total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and high density lipoprotein cholesterol (HDL-C) levels were not different for 8:0, cis-18:1, and trans-18:1, whereas 14:0 caused a significant rise in plasma TC, LDL-C, and HDL-C. LDL oxidation measurements showed that the lag phase of conjugated diene formation was longest for the trans-18:1 and cis-18:1 groups while rate of conjugated diene formation was lowest for the trans-18:1 and cis-18:1 groups. The trans-18:1- and cis-18:1-fed animals had significantly higher levels of LDL alpha-tocopherol relative to the 8:0- and 14:0-fed animals. Aortic fatty streak formation was highest for the 14:0- and 8:0-fed animals and lowest for the trans-18:1. In conclusion, the plasma lipid and antioxidant properties of trans-18:1 and cis-18:1 were comparable while the trans-18:1-fed hamsters had the least amount of early atherosclerosis. In addition, 8:0-fed animals unexpectedly had early atherosclerosis formation similar to the 14:0-fed animals.

The current study was designed to investigate the hypocholesterolemic and anti-atherogenic properties of soy lecithin beyond its fatty acid content. In experiment 1, 18 cynomolgus monkeys were divided into three groups of six and fed diets which approximated either the average American diet (AAD), the American Heart Association (AHA) Step I diet, or a modified AHA (mAHA) Step I diet containing 3.4% soy lecithin for 8 weeks. Plasma samples were collected from food-deprived monkeys and analyzed for total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), very low- and low-density lipoprotein cholesterol (non-HDL-C), and triglyceride (TG) concentrations. Group comparisons revealed that monkeys fed the mAHA Step 1 diet had significantly lower plasma TC (-46%) and non-HDL-C (-55%) levels compared to the AAD diet, whereas monkeys fed the AHA Step 1 diet had lesser reductions in plasma TC (-21%) and non-HDL-C (-18%) levels. The monkeys fed the mAHA Step I diet had significantly lower plasma TC (-32%) and non-HDL-C (-45%) compared to the monkeys fed the AHA step diet. Also, only the mAHA Step I diet significantly reduced pre-treatment plasma TC and non-HDL-C levels by - 39 and -51% respectively with no significant effect on plasma HDL-C or TG levels. In experiment 2, 45 hamsters were divided into three groups of 15 and fed the following three modified non-purified diets for 8 weeks: a hypercholesterolemic diet (HCD) containing 10%, coconut oil and 0.05%, cholesterol, HCD plus 3.4%, soy lecithin (+SL), or the HCD with added levels of linoleate and choline equivalent to the +SL diet but no lecithin (-SL). Plasma lipids were determined as in experiment 1 and aortas were perfusion-fixed and Oil Red O stained for morphometric analyses of fatty streak area. Relative to the HCD group, the +SL-treated hamsters had significantly lower plasma TC (-58%), non-HDL-C (-73%) and aortic fatty streak area (-90%). Relative to the -SL group, hamsters fed the +SL diet had significantly lower plasma TC (-33%), non-HDL-C (-50%) and significantly reduced aortic fatty streak area (-79%). In conclusion, the first experiment suggests that the cholesterol-lowering efficacy of the AHA Step I diet can be enhanced with the addition of soy lecithin without reducing plasma HDL-C levels. whereas the second experiment suggest that the hypocholesterolemic, and in particular, the anti-atherogenic properties of soy lecithin cannot be attributed solely to its linoleate content.

Saturated vegetable oils (coconut, palm, and palm kernel oil) containing predominantly saturated fatty acids, lauric (12:0) or myristic (14:0 and palmitic (16:0), raise plasma total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels in animals and humans, presumably by decreasing LDL receptor activity and/or increasing LDL-C production rate. Although stearic acid (18:0) is chemically a saturated fatty acid, both human and animal studies suggest it is biologically neutral (neither raising nor lowering) blood cholesterol levels. Although earlier studies indicated that medium chain fatty acids (8:0-10:0) were also thought to be neutral, more recent studies in animals and humans suggest otherwise. Unsaturated vegetable oils such as corn, soybean, olive, and canola oil, by virtue of their predominant levels of either linoleic acid (18:2) or oleic acid (18:1), are hypocholesterolemic, probably as a result of their ability to upregulate LDL receptor activity and/or decrease LDL-C production rate. Whether trans fatty acids such as trans oleate (t18:1), in hydrogenated products such as margarine, are hypercholesterolemic remains controversial. Studies in humans suggest that their cholesterol-raising potential falls between the native nonhydrogenated vegetable oil and the more saturated dairy products such as butter. Assessment of the magnitude of the cholesterolemic response of trans 18:1 is difficult because in most diet studies its addition is often at the expense of cholesterol-lowering unsaturated fatty acids, making an independent evaluation almost impossible.

Saturated vegetable oils (coconut, palm, and palm kernel oil) and fats (butter and lard) are hypercholesterolemic relative to monounsaturated and polyunsaturated vegetable oils. The increase in plasma low-density-lipoprotein-cholesterol (LDL-C) concentrations associated with consumption of saturated vegetable oils and fats is largely explained by a decrease in hepatic LDL receptor activity and an increase in the LDL-C production rate. Hepatic LDL receptor activity may be regulated by the messenger RNA concentration of the LDL receptor. The decrease in hepatic LDL receptor activity with saturated fat feeding is associated with decreased hepatic sterol O-acyltransferase activity and, therefore, a reduced inert pool of cholesteryl ester. A putative regulatory pool of cholesterol is increased with saturated fat feeding and suppresses LDL receptor activity, possibly through hepatic messenger RNA regulation. For most studies, an independent effect of a vegetable oil or fat could not be ascertained because there was no neutral control and at least two of the test oils or fats were varied. Animal data for the effects of individual fatty acids on plasma LDL-C concentrations and metabolism are sparse. The evidence suggests that caproic acid (6:0), caprylic acid (8:0), and capric acid (10:0) are neutral with respect to their LDL-C-raising properties and their ability to modulate LDL metabolism. Lauric acid (12:0), myristic acid (14:0), and palmitic acid (16:0) are approximately equivalent in their LDL-C-raising potential by reducing hepatic LDL receptor activity and increasing the LDL-C production rate, apparently via modulation of sterol O-acyltransferase activity. Stearic acid (18:0) appears to be neutral in its LDL-C-raising potential and how it affects LDL metabolism.

To determine the mechanisms whereby dietary fatty acids influence high density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I concentrations, ten cynomolgus monkeys were fed each of three experimental diets enriched in saturated (SAT), monounsaturated (MONO), or polyunsaturated (POLY) fatty acids in a crossover design consisting of three 13-week periods, with each animal serving as its own control. Each diet contained 30% of energy as fat with 0.22 mg cholesterol/kcal and differed solely by the isocaloric substitution of fatty acids as 18% of total energy calories. The replacement of dietary saturated fatty acids with either monounsaturated or polyunsaturated fatty acids, respectively, resulted in significant reductions of plasma total cholesterol (-17%; -30%), HDL cholesterol (-32%; -41%), and apo A-I (-37%; -44%) concentrations, while no significant differences were noted in plasma lipid or apo A-I concentrations when the MONO and POLY phases were compared. Although the MONO and POLY diets were similar in their effects on plasma lipids and apolipoproteins, the HDL of monkeys fed the POLY diet, as compared with either the SAT or the MONO diets, contained more cholesteryl ester and phospholipid but less total protein, resulting in a significantly lower total lipid to protein constituent ratio. Metabolic experiments revealed that the significantly lower plasma apo A-I concentrations observed during both the MONO and POLY phases relative to SAT were directly attributable to enhanced HDL apo A-I catabolism. Conversely, neither HDL apo A-I production rates nor hepatic apo A-I mRNA concentrations were significantly affected by dietary fatty acid perturbation in this study. Taken together, these data indicate that fractional catabolic rate is the predominant mechanism by which dietary fatty acids differentially modulate circulating concentrations of HDL apo A-I in this species when all other dietary variables are held constant.

Although studies have shown that saturated and polyunsaturated fats can mediate plasma lipid and apolipoprotein (apo) concentrations at the mRNA level, there is little data on the role of monounsaturated fats. We determined hepatic lipid and apo mRNA levels in 10 cynomolgus monkeys fed three diets that provided 30% of energy as fat with 0.1% cholesterol by weight and differed solely by the substitution of saturated, mono- and polyunsaturated fats as 60% of total fat energy. Total, LDL, and HDL cholesterol, as well as LDL apo B, HDL apo A-I and HDL total apo C concentrations, were reduced with the mono- and polyunsaturated fat diets relative to the saturated fat diet. Although fat saturation did not significantly affect hepatic apo A-I, B, C-II, or E mRNA abundance, hepatic apo C-III mRNA concentrations were uniformly lower (-23%, P < 0.01) with the mono- and polyunsaturated fat diets than with the saturated fat diet. Interestingly, liver triglycerides were significantly elevated with the monounsaturated fat diet relative to the saturated fat diet, but no other differences in hepatic lipids were noted among diets. Hepatic triglyceride composition was shown to reflect dietary fatty acid composition, with liver triglycerides enriched in myristic and palmitic fatty acids during the saturated fat diet, oleic acid during the monounsaturated fat diet and linoleic acid during the polyunsaturated fat diet. We conclude that dietary monounsaturated fats are comparable to polyunsaturated fats in their effects on hepatic lipid and apo mRNA levels in this species, with both unsaturated fats significantly reducing only hepatic apo C-III mRNA abundance relative to saturated fat.

Plasma lipoprotein(a) (Lp(a)) concentration is an independent risk factor for the development of premature coronary artery disease. Although the majority of available data indicates that circulating Lp(a) levels are under strict genetic regulation, there is some evidence that this parameter may be subject to dietary modification as well. The effects of dietary fat saturation on plasma Lp(a) levels and hepatic apolipoprotein(a) (apo(a)) mRNA abundance were examined in ten unrelated cynomolgus monkeys which were fed each of three experimental diets enriched in saturated (SAT), monounsaturated (MONO), or polyunsaturated (POLY) fatty acids in a crossover design consisting of three 13-week periods. Each diet contained 30% of calories as fat with 0.1% dietary cholesterol by weight and differed solely by the isocaloric substitution of fatty acids as 60% of total fat calories. The mean Lp(a) level for these animals during the SAT diet (13.4 +/- 2.4 mg/dl) was significantly greater as compared with those observed during the MONO (8.6 +/- 2.2 mg/dl, P < 0.0003) and POLY (9.3 +/- 2.1 mg/dl, P < 0.002) diets, while the difference noted between the MONO and POLY diets was nonsignificant. Hepatic apo(a) mRNA abundance was decreased in these animals during the MONO diet relative to both the SAT and POLY diets, with only the difference between the SAT and MONO diets achieving statistical significance (P < 0.02). Our data demonstrate that the substitution of dietary SATs with either MONOs or POLYs result in significant reductions of Lp(a) levels in these monkeys. However, only the MONO diet significantly decreased hepatic apo(a) mRNA levels relative to the SAT diet, suggesting that dietary MONOs and POLYs may differ in the manner by which they regulate plasma Lp(a) levels.

To determine the mechanisms whereby dietary fat saturation influences LDL cholesterol and apolipoprotein B concentrations, 10 cynomolgus monkeys were fed each of three experimental diets enriched in saturated, monounsaturated or polyunsaturated fatty acids in a crossover design consisting of three 13-wk periods. Each diet contained 30% of energy as fat with 0.05 mg cholesterol/kJ and differed solely by the isocaloric substitution of fatty acids as 60% of total fat energy. The replacement of dietary saturated fatty acids with either mono- or polyunsaturated fatty acids resulted in significant reductions of plasma total cholesterol (-17% and -30%, respectively), HDL cholesterol (-32% and -41%, respectively), apoA-1 (-37% and -44%, respectively), and apolipoprotein B (-28% and -36%, respectively) concentrations. Additionally, when dietary polyunsaturated fatty acids were substituted for saturated fatty acids, a 27% reduction in VLDL + LDL cholesterol was significant. Metabolic experiments suggested that the significantly reduced concentrations of apolipoprotein B observed during the monounsaturated and polyunsaturated fatty acid phases relative to the saturated fatty acid phase could not be entirely explained by changes in LDL apolipoprotein B clearance but rather were likely due to decreased LDL apolipoprotein B production rates. However, enhanced LDL apolipoprotein B catabolism accounted for the even greater reductions in VLDL + LDL cholesterol and apolipoprotein B concentrations observed during the polyunsaturated fatty acid phase vs. the monounsaturated fatty acid phase. Our data suggest that monounsaturated and polyunsaturated fatty acids lower apolipoprotein B concentrations by distinct mechanisms, with polyunsaturated fatty acids affecting LDL apolipoprotein B catabolism as well as production.

The effects of the long-term administration of the dietary fats coconut oil and corn oil at 31% of calories with or without 0.1% (wt/wt) dietary cholesterol on plasma lipoproteins, apolipoproteins (apo), hepatic lipid content, and hepatic apoA-I, apoB, apoE, and low density lipoprotein (LDL) receptor mRNA abundance were examined in 27 cebus monkeys. Relative to the corn oil-fed animals, no significant differences were noted in any of the parameters of the corn oil plus cholesterol-fed group. In animals fed coconut oil without cholesterol, significantly higher (P less than 0.05) plasma total cholesterol (145%), very low density lipoprotein (VLDL) + LDL (201%) and high density lipoprotein (HDL) (123%) cholesterol, apoA-I (103%), apoB (61%), and liver cholesteryl ester (263%) and triglyceride (325%) levels were noted, with no significant differences in mRNA levels relative to the corn oil only group. In animals fed coconut oil plus cholesterol, all plasma parameters were significantly higher (P less than 0.05), as were hepatic triglyceride (563%) and liver apoA-I (123%) and apoB (87%) mRNA levels relative to the corn oil only group, while hepatic LDL receptor mRNA (-29%) levels were significantly lower (P less than 0.05). Correlation coefficient analyses performed on pooled data demonstrated that liver triglyceride content was positively associated (P less than 0.05) with liver apoA-I and apoB mRNA levels and negatively associated (P less than 0.01) with hepatic LDL receptor mRNA levels. Liver free and esterified cholesterol levels were positively correlated (P less than 0.05) with liver apoE mRNA levels and negatively correlated (P less than 0.025) with liver LDL receptor mRNA levels. Interestingly, while a significant correlation (P less than 0.01) was noted between hepatic apoA-I mRNA abundance and plasma apoA-I levels, no such relationship was observed between liver apoB mRNA and plasma apoB levels, suggesting that the hepatic mRNA of apoA-I, but not that of apoB, is a major determinant of the circulating levels of the respective apolipoprotein. Our data indicate that a diet high in saturated fat and cholesterol may increase the accumulation of triglyceride and cholesterol in the liver, each resulting in the suppression of hepatic LDL receptor mRNA levels. We hypothesize that such elevations in hepatic lipid content differentially alter hepatic apoprotein mRNA levels, with triglyceride increasing hepatic mRNA concentrations for apoA-I and B and cholesterol elevating hepatic apoE mRNA abundance.

The mechanism(s) by which polyunsaturated fats reduce low density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B were investigated in 20 cebus monkeys (Cebus albifrons) fed diets containing corn oil or coconut oil as fat (31% of calories) with or without dietary cholesterol (0.1% by weight) for 3 to 10 years. Coconut-oil feeding compared to corn-oil feeding resulted in significant increases in levels of plasma total cholesterol (176%), very low density lipoprotein (VLDL)-LDL cholesterol (236%), high density lipoprotein (HDL) cholesterol (148%), apo B (78%), and apo A-I (112%). The addition of dietary cholesterol to corn oil compared to corn oil alone resulted in smaller, but significant, increases in levels of total cholesterol (44%), HDL cholesterol (40%), and apo A-I (33%). Although the increases in VLDL-LDL cholesterol were of similar magnitude (52%), they barely failed to reach statistical significance (p less than 0.08), while the changes in apo B levels were negligible. The addition of dietary cholesterol to coconut oil, compared to coconut oil alone, resulted in no significant changes in lipoprotein cholesterol or apoproteins, although levels of VLDL-LDL cholesterol and apo B values increased 22% and 16%, respectively. Although hepatic free cholesterol content was not altered by diet, coconut-oil compared to corn-oil feeding resulted in significant increases in hepatic cholesteryl esters (236%) and triglycerides (325%), the latter increasing still further when dietary cholesterol was added to coconut oil (563%). To further assess the effects of these dietary changes on LDL metabolism, radioiodinated normal and glucosylated LDL kinetics were performed. The production rate of LDL apo B was not altered by diet. With corn-oil feeding, 63% of LDL catabolism was via the receptor-mediated pathway. Coconut-oil compared to corn-oil feeding resulted in a 50% decrease in receptor-mediated LDL apo B fractional catabolic rate (FCR) and a 27% reduction in nonreceptor-mediated LDL apo B FCR. The addition of dietary cholesterol to corn oil, compared to corn oil alone, resulted in no significant effect on LDL apo B catabolism. The addition of dietary cholesterol to coconut oil, compared to coconut oil alone, was associated with no significant change in nonreceptor catabolism of LDL apo B but with a 58% decrease in receptor-mediated catabolism of LDL (p less than 0.059). The diet-induced alterations of LDL catabolism were significantly correlated with hepatic lipids, which were enriched in saturated fatty acids.(ABSTRACT TRUNCATED AT 400 WORDS)

In order to compare in vitro and in vivo aspects of lipid metabolism and lipoprotein secretion associated with the hyperlipemia of saturated fat feeding, gerbils were fed a diet containing 15% coconut oil or safflower oil for 6 weeks. In vitro incorporation of fatty acid was determined by measuring 14C-oleic acid incorporation into hepatic lipis in liver fasting gerbils following Triton WR1339 injection. The plasma lipoprotein profile was assessed by agarose electrophoresis. Coconut oil produced a hypertriglyceridemia and hypercholesterolemia associated with the appearance of very low density migrating lipoprotein, not seen with the safflower oil. Coconut oil also increased the hepatic triglyceride content, enhanced 14C-oleic acid incorporation into total lipid, and favored fatty acid incorporation into triglyceride; safflower oil facilitated esterification of oleic acid into phospholipid. Triton blockade of gerbils fed safflower oil resulted in twice the triglyceride secretion rate of those fed coconut oil. Our interpretation of the data is that dietary polyunsaturated fat favors incorporation of fatty acids into phospholipid, enhances both triglyceride secretion and the plasma transport and clearance of triglyceride and cholesterol and that the hyperlipemia of coconut oil feeding reflects a reduced metabolic clearnace of circulating lipid associated with that dietary fat.

In order to isolate the effects of the type of dietary fat from those of dietary cholesterol on the circulating pool of cholesterol, plasma lipoproteins were characterized in juvenile rhesus monkeys fed semipurified diets containing 31% of calories as corn oil or coconut oil. Half the diets contained 300 mg of cholesterol per 1000 kcal. The fatty acids of cholesteryl esters and phospholipids varied significantly with dietary fat such that saturated and monounsaturated fatty acids replaced polyunsaturated fatty acids in low-density lipoproteins (LDL) and high density-lipoproteins of rhesus monkeys fed coconut oil. Dietary cholesterol alone induced small but significant increases in the cholesteryl ester: triglyceride ratio in both very low-density lipoproteins and LDL. Whereas neither saturated fat (coconut oil) nor cholesterol alone substantially altered the plasma cholesterol concentration or lipoprotein profile, together these dietary components interacted synergistically to produce a significant elevation in plasma cholesterol. This was due primarily to a significant rise in the cholesteryl ester fraction of LDL, disproportionate to any change in LDL protein concentration. The data are consistent with current hypotheses that relate parameters of LDL turnover and clearance to their macromolecular structure and physicochemical characteristics.

Rhesus monkeys were fed corn or coconut oil-based diets for 3-6 mo to determine effects on the composition of all lipoprotein classes and on the metabolism of high density lipoproteins (HDL). Major findings included the following. Coconut oil feeding increased concentrations of all classes of plasma lipoproteins without altering lipoprotein size, suggesting an increase in particle number. The percentage of saturated fatty acids in the cholesteryl esters (CE) of low density lipoproteins (LDL) and HDL reached 40% with coconut oil feeding. This value probably constitutes a minimum estimate of the CE which were of intracellular rather than intraplasmic origin. The CE in LDL and HDL were nearly identical suggesting virtually complete equilibration by the core lipid transfer reaction. The CE in very low density lipoproteins, in contrast, were significantly more saturated than those in LDL and HDL irrespective of diet. Lower HDL levels on the corn oil diet were associated with higher fractional catabolic rates for both apolipoprotein A-I (0.42 vs. 0.31 d-1) and apolipoprotein A-II (0.45 vs. 0.30 d-1).

The influence of hypercholesterolemia on the triglyceride secretion rate was studied in both squirrel and cebus monkeys fed coconut oil, corn oil, or safflower oil. The triglyceride secretion rate (TGSR) was determined in vivo following the administration of Triton WR1339, which blocks the clearance of very low density lipoprotein (VLDL). Thus, the increase observed in circulating triglyceride after Triton administration presumably reflecte hepatic triglyceride (VLDL) secretion in the fasted state. The VLDL-TGSR was lowest in hypercholesterolemic monkeys and highest in those fed unsaturated fat diets and having a low serum cholesterol. In all instances, TGSR was inversely correlated with the plasma cholesterol concentration. While a definitive explanation for these observations must await further investigation, the possibility that circulating low density lipoprotein (LDL) acts to feed back on VLDL secretion is discussed. The decreased TGSR associated with the diet-induced cholesterolemia also implies clearance of VLDL is impaired under these conditions.

Lipid and apoprotein moieties of the plasma lipoproteins of Mongolian gerbils (Meriones unguiculatus) were compared in animals fed semipurified diets containing either coconut oil (COC) or safflower oil (SAF). COC-induced hypercholesterolemia was associated with elevations in very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL). Saturated fat feeding also resulted in th saturation of fatty acids of triglycerides and cholesteryl esters of VLDL and LDL, but had little effect on HDL fatty acids. Lipoprotein composition and size were not influenced by the type of dietary fat, suggesting that the hypercholesterolemia with saturated fat feeding was due to the circulation of a greater number of lipoprotein particles. The apoproteins of gerbil lipoproteins had molecular weights comparable to other animals. The relative amounts of apoproteins, particularly the apoC peptides, increased with dietary fat saturation.