Hydrogenation alternatives: effects of trans fatty acids and stearic acid versus linoleic acid on serum lipids and lipoproteins in humans.

The objective of this study was to compare the effects of linoleic acid (cis,cis-C18:2(n-6)) and its hydrogenation products elaidic (trans-C18:1(n-9)) and stearic acid (C18:0) on serum lipoprotein levels in humans. Twenty-six men and 30 women, all normolipemic and apparently healthy, completed the trial. Three experimental diets were supplied to every subject for 3 weeks each, in random order (multiple cross-over). The Linoleate-diet provided 12.0% of total energy intake as linoleic acid, 2.8% as stearic acid, and 0.1% as trans fatty acids. The Stearate-diet supplied 3.9 energy % as linoleic acid, 11.8% stearic acid, and 0.3% trans fatty acids. The Trans-diet provided 3.8 energy % as linoleic acid, 3.0% stearic acid, and 7.7% as monounsaturated trans fatty acids, largely elaidic acid (trans-C18:1(n-9)). Other nutrients were constant. Fasting blood was sampled at the end of each dietary period. Mean (+/- SD) serum LDL cholesterol was 109 +/- 24 mg/dl (2.83 +/- 0.63 mmol/l) on the Linoleate-diet. It rose to 116 +/- 27 mg/dl (3.00 +/- 0.71 mmol/l) on the Stearate-diet (change, 7 mg/dl or 0.17 mmol/l, P = 0.0008) and to 119 +/- 25 mg/dl (3.07 +/- 0.65 mmol/l) on the Trans-diet (change, 9 mg/dl or 0.24 mmol/l, P less than 0.0001). High density lipoprotein (HDL) cholesterol decreased by 2 mg/dl (0.06 mmol/l, P less than 0.0001) on the Stearate-diet and by 4 mg/dl (0.10 mmol/l, P less than 0.0001) on the Trans-diet, both relative to linoleic acid. Our findings show that 7.7% of energy (mean, 24 g/day) of trans fatty acids in the diet significantly lowered HDL cholesterol and raised LDL cholesterol relative to linoleic acid. Combination with earlier results (Mensink, R. P., and M. B. Katan. 1990. N. Engl. J. Med. 323: 439-445) suggests a linear dose-response relation. Replacement of linoleic acid by stearic acid also caused somewhat lower HDL cholesterol and higher LDL cholesterol levels. Hydrogenation of linoleic acid to either stearic or trans fatty acids produces fatty acids that may increase LDL and decrease HDL cholesterol relative to linoleic acid itself.     

Impact of hydrogenated fat on high density lipoprotein subfractions and metabolism

Relative to saturated fatty acids, trans-fatty acids/hydrogenated fat-enriched diets have been reported to increase low density lipoprotein (LDL) cholesterol levels and either decrease or have no effect on high density lipoprotein (HDL) cholesterol levels. To better understand the effect of trans-fatty acids/hydrogenated fat on HDL cholesterol levels and metabolism, 36 subjects (female, n = 18; male, n = 18) were provided with each of three diets containing, as the major sources of fat, vegetable oil-based semiliquid margarine, traditional stick margarine, or butter for 35-day periods. LDL cholesterol levels were 155 +/- 27, 168 +/- 30, and 177 +/- 32 mg/dl after subjects followed the semiliquid margarine, stick margarine, and butter-enriched diets, respectively. HDL cholesterol levels were 43 +/- 10, 42 +/- 9, and 45 +/- 10 mg/dl, respectively. Dietary response in apolipoprotein (apo) A-I levels was similar to that in HDL cholesterol levels. HDL(2) cholesterol levels were 12 +/- 7, 11 +/- 6, and 14 +/- 7 mg/dl, respectively. There was virtually no effect of dietary fat on HDL3 cholesterol levels. The dietary perturbations had a larger effect on particles containing apoA-I only (Lp A-I) than apoA-I and A-II (Lp A-I/A-II). Cholesterol ester transfer protein (CETP) activity was 13.28 +/- 5.76, 15.74 +/- 5.41, and 14.35 +/- 4.77 mmol x h(-1) x ml(-1), respectively. Differences in CETP, phospholipid transfer protein activity, or the fractional esterification rate of cholesterol in HDL did not account for the differences observed in HDL cholesterol levels.These data suggest that the saturated fatty acid component, rather than the trans- or polyunsaturated fatty acid component, of the diets was the putative factor in modulating HDL cholesterol response.     

Influence of short term dietary cholesterol and fat on human plasma Lp[a] and LDL levels.

The relationship between plasma levels of Lp[a] and LDL was examined using dietary regimens. In 81 normolipidemic male outpatients, dietary cholesterol was increased by consuming six eggs per day from a mean (SD) level of 311 (162) to 1430 (198) mg per day. Mean (SD) LDL-cholesterol levels increased from 102 (26) mg/dl to 120 (33) mg/dl (P less than 0.001), while mean (SD) Lp[a] levels were 5.5 (6.1) mg/dl on the basal diet and 5.6 (6.4) mg/dl on the cholesterol-rich diet. No significant correlation was observed between increases in either LDL-cholesterol or apolipoprotein B to Lp[a], nor was there any relationship between individual baseline levels of Lp[a] and dietary-induced changes of Lp[a]. Fourteen of the 81 participants were reexamined under strict nutritional control. Four diets with 40% of calories as fat, but differing in the type of fat and the amount of cholesterol, were administered sequentially to all subjects. As expected, mean (SD) LDL-cholesterol and apolipoprotein B levels were highest on the saturated fat, high cholesterol diet (112 (32) mg/dl and 79 (22) mg/dl) and lowest on the polyunsaturated fat, low cholesterol diet (77 (27) mg/dl and 53 (18) mg/dl). In contrast, mean Lp[a] levels did not significantly change among the four diets (range 4.2-4.9 mg/dl). No correlation of Lp[a] responses with changes in plasma lipids, apolipoproteins, or lipoproteins was observed on any diet. These data suggest that determinants of plasma Lp[a] levels are distinctly different from the determinants of plasma LDL levels in normolipidemic males.     

Dietary fat modulation of apoA-II metabolism and prevention of senile amyloidosis in the senescence- accelerated mouse

Senescence-accelerated mouse-prone (SAMP1; SAMP1@Umz) is an animal model of senile amyloidosis with apolipoprotein A-II (apoA-II) amyloid fibril (AApoAII) deposits. This study was undertaken to investigate the effects of dietary fats on AApoAII deposits in SAMP1 mice when purified diets containing 4% fat as butter, safflower oil, or fish oil were fed to male mice for 26 weeks. The serum HDL cholesterol was significantly lower (P < 0.01) in mice on the diet containing fish oil (7.4 +/- 3.0 mg/dl) than in mice on the butter diet (38.7 +/- 12.5 mg/dl), which in turn had significantly lower (P < 0.01) HDL levels than mice on the safflower oil diet (51.9 +/- 5.6 mg/dl). ApoA-II was also significantly lower (P < 0.01) in mice on the fish oil diet (7.6 +/- 2.7 mg/dl) than on the butter (26.9 +/- 7.3 mg/dl) or safflower oil (21.6 +/- 3.7 mg/dl) diets. The mice fed fish oil had a significantly greater ratio (P < 0.01) of apoA-I to apoA-II, and a smaller HDL particle size than those fed butter and safflower oil. Severe AApoAII deposits in the spleen, heart, skin, liver, and stomach were shown in the fish oil group compared with those in the butter and safflower oil groups (fish oil > butter > safflower oil group, P < 0.05). These findings suggest that dietary fats differ in their effects on serum lipoprotein metabolism, and that dietary lipids may modulate amyloid deposition in SAMP1 mice.     

Long-term effects of cis and trans monounsaturated (18:1) and saturated (16:0) fatty acids on the synthesis and secretion of apolipoprotein A-I- and apolipoprotein B-containing lipoproteins in HepG2 cells

The objective of this study was to compare the long-term effects of oleic (cis 18:1), elaidic (trans 18:1), and palmitic (16:0) acids on hepatic lipoprotein production, using HepG2 cells as an experimental model. The net accumulation in the medium of apolipoprotein A-I (apoA-I) was not significantly altered by fatty acids, whereas that of apoB was increased with oleic and elaidic acids. Oleic acid, and to a lesser extent elaidic and palmitic acids, increased the mass of triglycerides in the medium and the incorporation of [(3)H]glycerol into secreted triglycerides. The incorporation of [(14)C]acetate into cellular and secreted total cholesterol was stimulated by 96% and 83%, respectively, with elaidic acid but was not significantly modified by oleic or palmitic acid. Relative to oleic acid, the secretion of (14)C-labeled phospholipids and triglycerides was decreased 28% to 31% with elaidic and palmitic acids whereas that of free cholesterol and cholesteryl esters was enhanced 93% and 73%, respectively, with elaidic acid but remained unchanged with palmitic acid. Compared with oleic acid, elaidic acid stimulated the secretion of very low density lipoprotein cholesterol (VLDL-Chol), low density lipoprotein cholesterol (LDL-Chol), and high density lipoprotein cholesterol (HDL-Chol) by 43%, 70%, and 34%, respectively, whereas palmitic acid decreased VLDL-Chol but had no significant effect on LDL-Chol and HDL-Chol. The ratios of total cholesterol to HDL-Chol were 3.17, 3.60, and 3.25 with oleic, elaidic, and palmitic acids, respectively; the corresponding ratios of LDL-Chol to HDL-Chol were 0.87, 1.10, and 0.93, respectively. Compared with oleic and palmitic acids, the LDL and HDL particles secreted in the presence of elaidic acid contained higher levels of free cholesterol and cholesteryl esters and a lower content of phospholipids. The phospholipid-to-total cholesterol ratios of HDL were 1.05, 0.40, and 0.76 with oleic, elaidic, and palmitic acids, respectively.Our results indicate that in comparison with cis monounsaturated and saturated fatty acids, trans fatty acids have more adverse effects on the concentration and composition of lipoproteins secreted by HepG2 cells.     

Differential effects of saturated fatty acids on low density lipoprotein metabolism in the guinea pig.

Studies have shown that dietary fat saturation affects guinea pig plasma low density lipoprotein (LDL) levels by altering both LDL receptor-mediated catabolism and flux rates of LDL (Fernandez et al. 1992. J. Lipid Res. 33: 97-109). The present studies investigated whether saturated fatty acids of varying chain lengths have differential effects on LDL metabolism. Guinea pigs were fed 15% (w/w, 35% calories) fat diets containing either palm kernel oil (PK), 52% lauric acid/18% myristic acid; palm oil (PO), 43% palmitic acid/4% stearic acid; or beef tallow (BT), 23% palmitic acid/14% stearic acid. Plasma LDL cholesterol levels were significantly higher for animals fed the PK diet (P < 0.001) with values of 83 +/- 19 (n = 12), 53 +/- 8 (n = 12) and 44 +/- 16 (n = 10) mg/dl for PK, PO, and BT diets, respectively. The relative percentage composition of LDL was modified by fat type; however, LDL diameters and peak densities were not different between diets, indicating no effect of saturated fatty acid composition on LDL size. ApoB/E receptor-mediated LDL fractional catabolic rates (FCR) were significantly lower in animals fed the PK diet (P < 0.01) and LDL apoB flux rates were reduced (P < 0.01) in animals fed the BT diet. A correlation was found between plasma LDL levels and receptor-mediated LDL catabolism (r = -0.66, P < 0.01). A higher apoB/E receptor number (Bmax), determined by in vitro LDL binding to guinea pig hepatic membranes, was observed for animals fed BT versus PK or PO diets and Bmax values were significantly correlated with plasma LDL levels (r = -0.776, P < 0.001). These results indicate that saturated fatty acids of varying chain length have differential effects on hepatic apoB/E receptor expression and on LDL apoB flux rates which in part account for differences in plasma LDL cholesterol levels of guinea pigs fed these saturated fats.     

Reduction of cholesterol absorption by dietary oleinate and fish oil in African green monkeys.

To determine whether diets enriched in monounsaturated or n-3 fatty acids cause a reduction in cholesterol absorption relative to those more enriched in saturated fatty acids, we measured cholesterol absorption in 18 African green monkeys fed diets enriched in lard, oleinate (oleic acid-rich safflower oil), or fish oil at two levels of dietary cholesterol (0.05 vs. 0.77 mg/kcal). All animals were initially challenged with the lard, high cholesterol diet to ascertain their responsiveness to dietary cholesterol. Based on the results of this challenge, low versus high responders were equally distributed in assignation to the low (n = 6) and high (n = 12) cholesterol regimens. Within each level of dietary cholesterol animals consumed all three dietary fats in random sequences during three experimental phases each lasting 9-12 months with a monkey chow washout period between each phase, so that each animal served as its own control. During each dietary phase measurements of plasma lipids and cholesterol absorption were performed. The animals fed the higher versus lower level of dietary cholesterol had significantly higher plasma total cholesterol and low density lipoprotein (LDL) cholesterol concentrations and lower percentage cholesterol absorption; high density lipoprotein (HDL) cholesterol levels were not affected by the level of dietary cholesterol. Dietary fish oil resulted in a 20-30% reduction (P less than 0.01) in total plasma and LDL cholesterol and a 30-40% reduction (P less than 0.01) in HDL cholesterol concentrations compared to lard and oleinate regardless of the level of dietary cholesterol. At the high level of cholesterol intake, the oleinate and fish oil diets resulted in significantly lower percentage cholesterol absorption compared to the lard fat diet (35 +/- 2%, 34 +/- 3%, 41 +/- 4%, respectively). At the lower level of dietary cholesterol, percentage cholesterol absorption values were higher than those at the high cholesterol intake (45-52% vs. 34-41%) but were not affected by the type of dietary fat. There was a significant positive correlation between plasma LDL cholesterol concentrations and percentage cholesterol absorption for the oleinate and lard diets at the high level of dietary cholesterol and a significant inverse association between plasma HDL cholesterol and percentage cholesterol absorption. We conclude that the type of dietary fat can influence cholesterol absorption in African green monkeys and that oleinate and fish oil reduce cholesterol absorption relative to lard when a high amount of cholesterol (0.77 mg/kcal) is present in the diet.     

Effects on plasma lipoproteins of monounsaturated, saturated, and polyunsaturated fatty acids in the diet of African green monkeys

Work by other investigators has shown that an increase in dietary content of monounsaturated fatty acids can result in a decreased plasma low density lipoprotein (LDL) cholesterol concentration. This observation, combined with the epidemiologic evidence that monounsaturated fat-rich diets are associated with decreased rates of death from coronary heart disease, suggests that inclusion of increased amounts of mono-unsaturated fat in the diet may be beneficial. The present study was carried out in a primate model, the African green monkey, to evaluate the effects of dietary monounsaturated fat on plasma lipoprotein cholesterol endpoints. Two study periods were carried out in which the fatty acid compositions of the experimental diets were varied. All diets contained 35% of calories as fat. In the first experimental period, a mixture of fats was used to set the dietary fatty acid composition to be approximately 50-60% of the desired fatty acid, either saturated, monounsaturated, or polyunsaturated (n-6). In the second experimental period, pure fats were used (palm oil, oleic acid-rich safflower oil, and linoleic acid-rich safflower oil) to maximize the difference in fatty acid composition. The effects of the more exaggerated dietary fatty acid differences of period 2 were similar to those that have been reported in humans. For the group fed the diet enriched in monounsaturated fat compared to saturated fat, whole plasma and LDL cholesterol concentrations were significantly lower while high density lipoprotein (HDL) cholesterol concentrations were not affected. For the group fed the diet enriched in polyunsaturated fat compared to saturated fat, both LDL and HDL cholesterol concentrations were significantly lower than in the group fed saturated fat. LDL cholesterol concentrations were comparable in the monounsaturated and polyunsaturated fat groups and the percentage of cholesterol in LDL was lowest in the monounsaturated fat fed group. Trends were similar for the mixed fat diets, although no statistically significant differences in plasma lipoprotein endpoints could be attributed to monounsaturated fatty acids in this dietary comparison. Since effects on plasma lipoproteins similar to those seen in humans were identified in this primate model, relevant mechanisms for the effects of dietary fatty acids on lipoprotein endpoints related to coronary artery atherosclerosis, per se, can subsequently be examined.     

Increased beef consumption increases apolipoprotein A-I but not serum cholesterol of mildly hypercholesterolemic men with different levels of habitual beef intake

The objective of this research was to compare the effects of a lean beef enriched in oleic acid to a beef that is typical of the commercial beef consumed in the United States. Ten mildly hypercholesterolemic men, ages 34-58 years old, were selected from the Texas A&M University faculty and staff. Subjects were randomly assigned to one of two diets for a 6-week duration followed by a crossover after a 4-week habitual diet washout period. Diets were consumed daily for a 6-week study period. Participants substituted lean beef obtained from Wagyu bullocks or commercial beef for the meat typically consumed. Total cholesterol, apolipoproteins A-I and B, triacylglycerols, and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol were measured in serum samples collected weekly. Beef type had no effect on any measured variable. There were no significant differences between baseline HDL or LDL cholesterol concentrations after the consumption of the beef test diets. Apolipoprotein A-I, serum glucose, and uric acid concentrations were elevated by the additional dietary beef. Analysis of records of customary diets indicated that one group consumed 160 g of beef daily, whereas the other group consumed only 26 g of beef daily. Therefore, post hoc analyses tested the habitual beef intake x treatment time interaction. LDL cholesterol concentration was markedly higher in the group with low habitual beef intake (180 vs 144 mg/dl), and HDL cholesterol was slightly higher (44 vs 40 mg/dl; post-test values) than for the group with high habitual beef intake, but there were no habitual intake x time interactions for LDL or HDL cholesterol. Creatinine and blood urea nitrogen concentrations also were greater in the individuals habitually consuming less beef. This study had three important findings: i) a lean beef source enriched with oleic acid was no different from commercial beef in its effect on lipoprotein fractions; ii) neither previous level of beef intake nor baseline LDL cholesterol concentration influenced the serum cholesterol response to added dietary beef, which was negative; and iii) apolipoprotein A-I, but not HDL or LDL cholesterol, was sensitive to the additional dietary beef.     

Studies on the effect of dietary fish oil on the physical and chemical properties of low density lipoproteins in cynomolgus monkeys

To determine the effect of isocaloric substitution of dietary fish oil for lard on the physical and chemical properties of plasma low density lipoproteins (LDL), ten adult male cynomolgus monkeys were fed diets containing 11% (by weight) fish oil or lard in a crossover study consisting of two 15-week periods with a 6-week washout period in between. The atherogenic diets contained 40% of calories as fat with 0.26 mg cholesterol/kcal. Periodic measurements of plasma lipids were made throughout the study and a large blood sample was taken near the end of each 15-week period for LDL isolation and characterization, and for quantification of plasma apolipoproteins. Values for both studies were combined (mean +/- SE; n = 10) by diet. Significantly lower high density lipoprotein (HDL) cholesterol (28 +/- 2 vs. 57 +/- 8 mg/dl), apoA-I (53 +/- 11 vs. 88 +/- 7 mg/dl), and apoE (4.2 +/- 0.9 vs. 8.2 +/- 1.5 mg/dl) concentrations were found when the animals were consuming the fish oil versus the lard diet, respectively, but total plasma cholesterol (408 +/- 35 vs. 416 +/- 14 mg/dl), LDL cholesterol (356 +/- 34 vs. 331 +/- 17 mg/dl), and apoB (227 +/- 35 vs. 205 +/- 23 mg/dl) levels were not affected. LDL size was smaller during fish oil feeding (4.2 +/- 0.1 vs. 4.9 +/- 0.1 g/mumol) and LDL particle concentration was greater (2.3 +/- 0.2 vs. 1.8 +/- 0.1 microM). During fish oil feeding LDL cholesteryl esters (CE) and phospholipids (PL) were enriched in n-3 fatty acids and were relatively poor in 18:1 and 18:2 LDL CE transition temperature was about 11 degrees C lower during fish oil feeding (32 +/- 1 vs. 44 +/- 0.5 degrees C) and was positively correlated with the number of saturated, monoun-saturated, and n-6 polyunsaturated CE molecules per LDL. The results suggested that the range of transition temperatures among individual animal LDL was primarily determined by the number of monounsaturated CE, and the accumulation of n-3 polyunsaturated CE in LDL during fish oil feeding uniformly lowered the transition temperature of the LDL particle. There was a significant decrease in the percentage of LDL phosphatidylcholine (59 +/- 1 vs. 72 +/- 1%) and an increase in lysophosphatidylcholine (13 +/- 1 vs. 5 +/- 1%) and sphingomyelin (22 +/- 1 vs. 17 +/- 1%) during fish oil feeding relative to that of lard.(ABSTRACT TRUNCATED AT 400 WORDS)     

A residential study comparing the effects of diets rich in stearic acid, oleic acid, and linoleic acid on fasting blood lipids, hemostatic variables and platelets in young healthy men

Dietary fat is known to influence the variables of blood coagulation and fibrinolysis associated with vascular disease. However, the role of fat content and/or fat composition of the diet in this regard is still not well understood. In the present study, we investigated the effects of three isoenergic diets of differing fat composition in nine healthy young men in a strictly controlled residential study. Subjects consumed the three experimental diets for periods of 2 weeks each, separated by a washout period of at least 5 weeks in a randomized crossover design. The diets provided 38% of total energy intake as fat, 45% as carbohydrate, and 17% as protein, and differed only with respect to the fatty acid composition (stearic acid-rich diet: 34.1% stearic acid, 36.6% oleic acid; oleic acid-rich diet: 65.8% oleic acid; linoleic acid-rich diet: 36.5% linoleic acid, 38% oleic acid). Blood samples were collected at the beginning and at the end of each dietary period from fasted subjects for determination of factor VII coagulant activity (FVIIc), activated factor VII (FVIIa), factor VII antigen (FVIIag), tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor type 1 (PAI-1) activity, fibrinogen, prothrombin fragment 1+2 (F(1+2)), and plasma lipids. There were no significant differences between diets in fasting plasma concentrations of FVIIc, FVIIa, FVIIag, fibrinogen, F(1+2), PAI-1 activity, and tPA activity. Plasma concentrations of lipids (high density lipoproteins, low density lipoproteins, triacylglycerols, and total cholesterol) were also unaffected. Although there were no changes in platelet aggregation response and membrane fluidity observed in any of the diets, increased anti-aggregatory prostaglandin E(1) binding to platelet membranes was observed only in the case of linoleic acid-rich diet. In conclusion, diets with very different fatty acid compositions, at 38% of energy as fat intake, did not significantly influence blood coagulation, fibrinolysis, or blood lipids in the fasting state in young healthy men.     

Measurment of rhesus monkey (Macaca mulatta) apolipoprotein B in serum by radioimmunoassay: comparison of immunoreactivities of rhesus and human low density lipoproteins.

A sensitive and specific double antibody radio-immunoassay for the major apolipoprotein (apoB) of rhesus (Macaca mulatta) serum very low density lipoprotein (VLDL) and low density lipoprotein (LDL) is described. The anti-serum was raised to LDL (d 1.030-1.040 g/ml) and the LDL(2) (d 1.020-1.050 g/ml) was labeled with (125)I by the chloramine-T or iodine monochloride method. The assay, which was sensitive to 0.02-0.5 micro g of LDL(2), had an inter-assay coefficient of variation of 4.5%. This assay was successfully used to measure apoB in the whole serum and low density lipoproteins of control monkeys maintained on a standard Purina monkey chow (PMC) diet and of three groups of monkeys fed atherogenic diets: an "average American diet," a 25% peanut oil and 2% cholesterol-supplemented PMC diet, and a 25% coconut oil and 2% cholesterol-supplemented PMC diet. The control monkeys (n = 13) had a serum cholesterol of 146 +/- 28 mg/dl and an apoB of 50 +/- 18 mg/dl. In the monkeys maintained on the atherogenic diets the serum apoB was elevated: 103 +/- 28 mg/dl (American), 102 +/- 35 mg/dl (peanut oil), and 312 +/- 88 mg/dl (coconut oil). The values for serum total cholesterol were 333 +/- 65 mg/dl (American), 606 +/- 212 mg/dl (peanut oil), and 864 +/- 233 mg/dl (coconut oil) and were elevated relative to controls (P < 0.001). For each of the diets, total serum cholesterol correlated with serum apoB (P < 0.001). The slopes of the regression lines of serum apoB vs. cholesterol for the monkeys on the PMC, American, and coconut oil diets were similar (m = 0.531, 0.401, and 0.359, respectively), but differed from that of monkeys on the peanut oil diet (m = 0.121). The immunoreactivities of rhesus and human LDL were compared using specific antisera raised against these antigens. In homologous assay systems, monkey and human LDL exhibited unique immunological determinants. The same results were obtained with the delipidated preparations of the two LDLs using antisera raised against either monkey or human apoB. Crossover studies using a heterologous tracer with each anti-serum resulted in the selection of a specific population of antibodies directed against antigenic sites shared by these two LDL species.     

Differential effects of cis and trans fatty acid isomers, oleic and elaidic acids, on the cholesteryl ester transfer protein activity.

In a previous publication (Lagrost, L. and Barter, P.J. (1991) Biochim. Biophys. Acta 1085, 209-216), saturated and cis unsaturated non-esterified fatty acids have been shown to modulate the rate at which cholesteryl esters are transferred from high-density lipoproteins (HDL) to low-density lipoproteins (LDL) in the presence of the human cholesteryl ester transfer protein (CETP). In the present report, the effects of cis (oleic acid) and trans (elaidic acid) monounsaturated isomers on the CETP-mediated transfer of cholesteryl esters between HDL and LDL were compared. Mixtures of human LDL and HDL3, containing or not radiolabelled cholesteryl esters, were incubated at 37 degrees C with CETP in the presence or in the absence of either stearic (18:0), oleic (18:1 cis) or elaidic (18:1 trans) acids. It was observed that oleic acid and elaidic acid had different effects on the CETP-mediated redistribution of radiolabelled cholesteryl esters as well as on the net mass transfer of cholesterol from HDL3 to LDL. In particular, at high non-esterified fatty acid/lipoprotein ratio, the transfer of cholesteryl esters was significantly inhibited by the cis isomer and increased by the trans isomer.     

Effect of dietary cis and trans fatty acids on serum lipoprotein[a] levels in humans.

Serum lipoprotein[a] (Lp[a]) is a strong risk factor for coronary heart disease. We therefore examined the effect of dietary fatty acid composition on serum Lp[a] levels in three strictly controlled experiments with healthy normocholesterolemic men and women. In Expt. I, 58 subjects consumed a control diet high in saturated fatty acids for 17 days. For the next 36 days, 6.5% of total energy intake from saturated fatty acids was replaced by monounsaturates plus polyunsaturates (monounsaturated fatty acid diet; n = 29) or by polyunsaturates alone (polyunsaturated fatty acid diet; n = 29). Both diets caused a slight, nonsignificant, increase in median Lp[a] levels, with no difference between diets. In Expt. II, 10% of energy from the cholesterol-raising saturated fatty acids (lauric, myristic, and palmitic acid) was replaced by oleic acid or by trans-monounsaturated fatty acids. Each of the 59 participants received each diet for 3 weeks in random order. The median level of Lp[a] was 26 mg/l on the saturated fatty acid diet; it increased to 32 mg/l (P less than 0.020) on the oleic acid diet and to 45 mg/l (P less than 0.001) on the trans-fatty acid diet. The difference in Lp[a] between the trans-fatty acid and the oleic acid diets was also highly significant (P less than 0.001). Expt. III involved 56 subjects; all received 8% of energy from stearic acid, from linoleic acid, or from trans-monounsaturates, for 3 weeks each. All other nutrients were equal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Trans fatty acids alter the lipid composition and size of apoB-100-containing lipoproteins secreted by HepG2 cells

This study was conducted to determine the secretion rate and composition of lipoproteins secreted by HepG2 cells as influenced by the type of fatty acid present in the incubation medium. Cells were preincubated for 24 h with palmitic, oleic, elaidic, linoleic or conjugated linoleic acid (CLA), and the lipoproteins secreted during a subsequent incubation period of 24 h were collected for analysis. The secretion rate of apolipoprotein B-100 (apoB) was significantly greater in HepG2 cells preincubated with elaidic acid compared with those preincubated with palmitic or oleic acid; apoB secretion was greater in cells preincubated with CLA compared with those preincubated with linoleic acid. The lipid composition of secreted lipoproteins was also influenced by fatty acid treatment, resulting in significantly smaller lipoprotein particles secreted by cells preincubated with elaidic acid and CLA compared with those secreted by cells treated with oleic acid and linoleic acid, respectively. Our results are relevant to human metabolism for the following reasons: (1) the size of plasma low-density lipoproteins (LDLs) is determined, at least in part, by the composition of apoB-containing lipoproteins secreted by the liver; (2) small plasma LDL particles are associated with an increased risk of coronary heart disease; and (3) specific dietary fatty acids can affect the composition and size of plasma LDLs, thereby imparting a relative atherogenicity to plasma LDLs independent of LDL cholesterol concentration. The present study therefore suggests that elaidic acid and CLA promote the hepatic secretion of small apoB-containing lipoproteins, which could lead to an increased production of small plasma LDL particles.     

Influence of partial replacement of starch by sucrose in high fat-cholesterol diet on serum lipoprotein responses of cynomolgus monkeys

The influence of partial replacement of starch by sucrose on dietary cholesterol-induced serum lipoprotein responses was examined in 10 male cynomolgus monkeys (Macaca fascicularis). In a crossover design two semipurified diets provided either starch or starch and sucrose (1:1) as carbohydrate (49% by calories) with 0.4 mg cholesterol/kcal. Six weeks of starch + sucrose diet resulted in significantly reduced levels (mean +/- SE, mg/dl) of serum total cholesterol (264 +/- 9 vs 244 +/- 8) and apo B (110 +/- 6 vs 96 +/- 6) when compared with starch diet, whereas serum triglyceride levels remained similar between diets. With respect to changes in lipids and apolipoproteins (A-I or B) of very low (VLDL), low (LDL), intermediate (IDL), and high (HDL) density lipoproteins, starch + sucrose diet significantly increased VLDL-apo B (+34%), and decreased LDL-cholesterol (-18%) and LDL-apo B (-15%) as compared with starch alone; no differences were found in IDL and HDL between diets. The relative proportion of starch to sucrose in a diet appears to influence the magnitude of response of lipoproteins to dietary cholesterol.     

Dietary palmitic acid (16:0) enhances high density lipoprotein cholesterol and low density lipoprotein receptor mRNA abundance in hamsters

In order to examine the qualitative effect of different fats and specific fatty acids on plasma lipids and lipoprotein metabolism, six low fat, cholesterol-free diets were fed to young male hamsters (10/group) for a 4-week period. Fat blends were formulated with coconut oil, palm oil, soybean oil, high oleic acid safflower oil, butter, corn oil, and canola oil. Diets contained 13% energy as fat and dietary polyunsaturate/saturate ratios ranged from 0.12 to 1.04, one of which incorporated the American Heart Association-recommended concentrations of saturates, monoenes, and polyenes and another reflected the current American Fat Blend. In three diets the polyunsaturate/monounsaturate/saturate ratio was held constant while only the 12:0, 14:0, and 16:0 were varied. Plasma lipoproteins and apoproteins were assessed in conjunction with the abundance of specific hepatic and intestinal mRNA for the low density lipoproteins (LDL) receptor and various apolipoproteins associated with cholesterol metabolism. The plasma cholesterol response was lowest with the American Heart Association blend and equally elevated by the more saturated, low polyene diets (polyunsaturate/saturate, 0.12-0.38). Replacing 12:0 plus 14:0 from coconut oil with 16:0 as palm oil induced a significant increase in high density lipoprotein (HDL) cholesterol with a trend toward decreased LDL. These shifts in lipoprotein cholesterol were corroborated by measures of the LDL/HDL ratio, the plasma apolipoprotein B/apolipoprotein A1 ratio, and differences in the synthesis of apolipoproteins and the LDL receptor based on estimates of the mRNA for these proteins in the liver and gut, using specific cDNA probes for apolipoprotein A1, apolipoprotein B, apolipoprotein E, and the LDL receptor. Although it has been suggested that dietary polyenes lower total plasma cholesterol, including HDL, and that saturated fat increases both these pools of cholesterol, the current data represents the first evidence that a specific saturated fatty acid, i.e., palmitic acid, may enhance HDL production.     

Cholesterol-free diet with a high ratio of polyunsaturated to saturated fatty acids in heterozygous familial hypercholesterolemia: significant lowering effect on plasma cholesterol

We have studied the effect of diet therapy on plasma lipoprotein metabolism in heterozygous familial hypercholesterolemia. Seven patients with a mean plasma cholesterol concentration of 323 +/- 67 mg/dl were hospitalized and kept on a cholesterol-free diet for as long as 11 days without any medication. The content of dietary cholesterol was approximately 1.4 mg a day, and dietary fat, carbohydrate and protein comprised 18.0, 69.2 and 12.8% of calories, respectively. The ratio of polyunsaturated to saturated fatty acids (P/S) was 3.1. At the end of the study period, plasma cholesterol was lowered by 14.2%, from 323 to 277 mg/dl, and low density lipoprotein (LDL) cholesterol by 17.5% from 229 to 189 mg/dl. Using density gradient ultracentrifugation, the major change in LDL cholesterol was found to be in those fractions with a mean density between 1.034 and 1.042, where cholesterol concentrations decreased from 132 to 87 mg/dl (34%). These results indicate that diet therapy with free-cholesterol and a high ratio of P/S is highly effective in controlling plasma cholesterol levels in heterozygous familial hypercholesterolemia.     

Hydrogenated fat consumption affects cholesterol synthesis in moderately hypercholesterolemic women

To determine mechanisms by which hydrogenated fat influences plasma lipid levels, 14 women (65;-71 yrs with LDL-C >/= 130 mg. dl(-)(1)) consumed, for 5-week periods each, a baseline (BL) diet (39% kcal fat, 164 mg chol. 1000 kcal(-)(1)) and reduced fat diets (30% kcal) where two-thirds of the fat was either soybean oil (SO), low trans squeeze (SQM), medium trans tub (TM), or high trans stick (SM) margarines, or butter (BT). Plasma lipid levels were analyzed at the end of each phase. Fractional synthesis rates (FSR) in pools/day (p. d(-)(1)) and absolute synthesis rates (ASR) in grams/day (g. d(-)(1)) of free cholesterol (FC) were measured using the deuterium incorporation methodology. Plasma total (P < 0.01) and low density lipoprotein (P < 0.05) cholesterol levels increased with increasing degree of hydrogenation or saturated fat intake. High density lipoprotein cholesterol levels (P < 0.05) were lowest on the SM diet when compared to the BT diet. Low trans SQM (0.081 +/- 0.019 p. d(-)(1)) and medium trans TM (0.086 +/- 0.029 p. d(-)(1)) diets elicited responses similar to the SO (0.078 +/- 0.024 p. d(-)(1)) diet, whereas high trans SM (0.053 +/- 0.029 p. d(-)(1)) diet mimicked the BT (0.062 +/- 0.017 p. d(-)(1)) and high fat BL (0.053 +/- 0.023 p. d(-)(1)) diet in its suppression (P < 0.05) of FSR-FC. ASR-FC, which is an approximation of the daily production of newly synthesized cholesterol, showed a trend similar to the FSR-FC data. These results indicate that reduced synthesis is not responsible for the higher plasma TC levels seen with consumption of the SM, BT, and BL diets, and suggest that another mechanism, possibly impairment of the catabolic pathway of cholesterol, is involved.     

Effects of dietary alpha linolenic acid on cholesterol metabolism in male and female hamsters of the LPN strain

N-3 polyunsaturated fatty acids and estrogens are recognized as protective factors of atherosclerosis, however their interactions on cholesterol metabolism remain unclear. Male and female hamsters were fed for 9 weeks diets containing 12.5% lipids and rich in either alpha-linolenic acid ("linseed" diet) or saturated fatty acids ("butter" diet). Hamsters fed the "linseed" diet exhibited lower plasma concentrations of cholesterol (-29%), total LDL (-35%) and HDL (-17%), glucose (-20%), insulin (-40%) and of the LDL-cholesterol/HDL-cholesterol ratio (-27%) than those fed the "butter" diet. In the liver, cholesterol content was 2.7-fold lower in response to the "linseed" diet, whereas the concentration of HDL receptor (SR-BI) and the activities of HMGCoA reductase and cholesterol 7alpha-hydroxylase were 30 to 50% higher than with the "butter" diet. By contrast, the LDL receptor concentration did not vary with the diet. Females exhibited higher concentration of LDL (+24%), lower concentration of plasma triglycerides (-34%), total VLDL (-46%) and VLDL-cholesterol (-37%) and of biliary phospholipids (-19%). Besides, there was also an interaction between gender and diet: in males fed the "butter" diet, plasma triglycerides and VLDL concentration, were 2 to 4 fold higher than in the other groups. These data suggest that gene and/or metabolic regulations by fatty acids could interact with that of sex hormones and explain why males are more sensitive to dietary fatty acids.