Bile acid and very low density lipoprotein production by cultured hepatocytes from hypo- orhyperresponsive rabbits fedcholesterol

Two groups of rabbits, either hyperresponsive or hyporesponsive to dietary cholesterol, wereselected after ten weeks of cholesterol feeding (0.2 g cholesterol/kg body weight per day). Bile acids and very low density lipoprotein (VLDL) production were determined in primary hepatocyte cultures from control, hyper- and hyporesponsive rabbits. Free cholesterol and cholesteryl ester contents in hepatocytes of the hyperresponsive rabbits was significantly increased. In contrast, lipid composition in hepatocytes of the hyporesponders was similar to that of control cells. Cholic acid was the predominant bile acid in the culture medium of hepatocytes together with small amounts of chenodeoxycholic and deoxycholic acids. The rate of cholic acid production by hepatocytes in the hyporesponsive group was two times higher than that in the hyperresponsive group. Bile acid production by control hepatocytes was slightly higher than in the hyperresponsive group. In contrast, secretion of VLDL cholesteryl ester was significantly increased by hepatocytes of the hyperresponsive rabbits. Similar differences, in bile acid production were found between hypo- and hyperresponsive rabbits selected after five days of cholesterol feeding and subsequent maintenance on a low cholesterol diet for a period of one month. The results suggest that the increased rate of bile acid production could contribute to the apparent resistance of hyporesponders to the atherogenic diet.     

Influence of rabbit milk upon cholesterolaemic response of offspring of rabbits

The milk lipids from the dams of two strains of rabbits differing in their cholesterolaemic response, one hyperresponsive and one hyporesponsive to dietary cholesterol, were analyzed. The hyperresponsive dams had significantly higher (P<0.05) cholesterol and phospholipid concentrations than the hyporesponsive dams but similar triglyceride concentrations. Cross fostering experiments with hyporesponsive and hyperresponsive offspring were carried out. Offspring from hyporesponsive parents suckled on hyper-responsive dams resembled hyperresponsive offspring in their cholesterolaemic response. However, offspring from hyper-responsive parents responded as hyper-responsive whether they were raised on their natural dams or on foster hyporesponsive dams. We conclude that the trait for hyperresponder characteristics is un-influenced by rabbit milk, while the trait for hyporesponder characteristics is dependent upon the cholesterol and phospholipid concentrations in milk.     

The hypercholesterolemic effect of dietary coconut fatversus corn oil in hypo- or hyperresponsive rabbits is not exerted through influencing cholesterol absorption

In two inbred strains of rabbits with high or low response of plasma cholesterol to dietary saturatedversus polyunsaturated fatty acids, the efficiency of intestinal cholesterol absorption was measured. The feeding of a cholesterol-free purified diet containing saturated fatty acids in the form of coconut fat, when compared with a diet containing corn oil as polyunsaturated fatty acids, did not influence the efficiency of cholesterol absorption in the two rabbit strains. Irrespective of the dietary fat source, the hyperresponsive rabbits absorbed cholesterol more efficiently. It is concluded that the hypercholesterolemic effect of dietary coconut fatversus corn oil is not exerted by influencing cholesterol absorption.     

Effects of dietary casein and soy protein on metabolism of radiolabelled low density apolipoprotein B in rabbits

Rabbits fed semipurified diets containing casein have elevated plasma cholesterol levels compared to those fed soy protein. As part of continuing studies on the mechanism of casein-induced hypercholesterolemia, two groups of six rabbits were fed these diets for 14 to 16 weeks. Animals fed the casein diet were found to have significantly higher plasma concentrations of protein, cholesterol, triacylglycerol, phospholipid and apolipoprotein B (apo B) associated with low density lipoprotein (LDL) than those fed the soy protein diet. Kinetic studies showed that the fractional catabolic rate of LDL-apo B was significantly lower in animals fed casein than in those fed soy protein regardless of whether the tracer LDL was obtained from donors fed casein or soy protein. The production rate of LDL-apo B was higher in casein-fed animals but this was not statistically significant. These results show that the efficiency of removal of LDL is significantly reduced in animals fed casein compared to those fed soy protein, and that the source of LDL did not affect the efficiency of its subsequent removal. The acumulation of LDL in casein-fed animals is consistent with down-regulation of the LDL receptor.     

Increases in hyperlipoproteinemia,disturbances in cholesterol metabolism and atherosclerosis induced by dietary restriction in rabbits fed a cholesterol-rich diet

The influence of dietary restriction on cholesterol transport and metabolism was investigated in rabbits given standard or cholesterol-rich diets (0.2 g cholesterol/kg body weight daily) eitherad libitum or with 50% caloric ration. Dietary restriction which has only a slight influence in control rabbits markedly aggravated the disturbances induced by exogenous cholesterol. With limited feeding, control rabbits presented a moderate increase in plasma cholesterol, whereas marked aggravation of hypercholesterolemia was observed in cholesterol-fed rabbits. Analysis of the lipoprotein profile showed that the excess of plasma cholesterol with the restricted cholesterol-rich diet corresponded to an increase in the concentration of very low density lipoprotein (VLDL) and low density lipoproteins (LDL) without any additional changes in the composition of these lipoproteins. No significant change appeared in the high density lipoprotein (HDL) concentration. The parameters of cholesterol metabolism were determined, from the curves of [³H] cholesterol radioactivity decrease, using a two-pool model. The increase in cholesterol turnover rate induced by the cholesterol-rich diet was accentuated by dietary restriction, whereas rabbits on standard restricted diet showed a slight decrease. The large increase in the size of both pools A and B in cholesterol-fed rabbits was even more pronounced with limited feeding. Dietary restriction induced additional accumulation of cholesterol in the aortic wall and the grade of the lesions was also aggravated.     

Regulation of very low density lipoprotein apo B metabolism by dietary fat saturation and chain length in the guinea pig

Studies investigated the effects of dietary fatty acid composition and saturation on the regulation of very low density lipoprotein (VLDL) apo B flux, clearance, and conversion to low density lipoprotein (LDL) in guinea pigs fed semipurified diets containing 15% (w/w) corn oil (CO), lard (LA), or palm kernel oil (PK). Plasma cholesterol levels were highest with dietary PK (3.1±1.0 mmol/L) followed by LA (2.4±0.4 mmol/L) and CO (1.6±0.4 mmol/L) intake. VLDL particles were larger (P<0.05) in the LA (78±7 nm) and PK (69±10 nm) groups compared to animals fed CO (49±5 nm). VLDL-apo B fractional catabolic rates (FCR) were highest in guinea pigs fed the LA diet (P<0.05) and VLDL apo B flux, estimated from VLDL ¹²⁵I-apo B turnover kinetics, were higher in LA compared to PK or CO fed guinea pigs. In the case of PK consumption, the kinetic estimates of VLDL apo B flux significantly underestimated rates compared to direct VLDL apo B secretion measurements and LDL turnover analyses. These data demonstrate that differences in the composition and amount of saturated fatty acids have differential effects on VLDL apo B flux, catabolism, and conversion to LDL which, together with changes in LDL receptor-mediated catabolism, determine plasma LDL cholesterol levels in guinea pigs. The data also indicate that kinetic analysis of VLDL metabolism in PK fed animals is inaccurate possibly due to the presence of a small, nonequilibrating pool of newly synthesized VLDL which is rapidly converted to LDL.     

Effect of modified dairy fat on postprandial and fasting plasma lipids and lipoproteins in healthy young men

Fatty acid profile of milk fat can be modified by cow feeding strategies. Our aim was postprandially and after 4 wk to compare the effect of a modified milk fat (M diet) [with 16% of the cholesterolemic saturated fatty acid (C12–16) replaced by mainly oleic and stearic acids] with the effect of D diet, including a conventional Danish milk fat on plasma lipids and lipoproteins. A side effect of the cow feeding regime was a 5% (w/w) increase in trans fatty acid in M diet. Eighteen subjects were fed for two periods of 4 wk strictly controlled isoenergetic test diets with 40% of energy from total fat and the same content of dietary cholesterol in a randomized study with cross-over design. Contrary to expectations, fasting low density lipoprotein (LDL) cholesterol concentration did not differ after the experimental periods. However, M diet resulted in a higher fasting total triacylglycerol concentration compared to D diet (P=0.009). Postprandial samples were taken at two different occasions (i) at day 21, after breakfast and lunch and (ii) on the last day of the study 2, 4, 6, and 8 h after a fat load. Postprandial plasma triacylglycerol and chylomicron triacylglycerol showed higher peak values after D diet than M diet (interaction effect, diet × times P<0.05). In conclusion, M diet did not lower LDL cholesterol compared to D diet. Thus any cholesterol-lowering effect of oleic and stearic acids may have been obscured by the high content of cholesterol-raising saturated fatty acids in milk fat. A higher content of the trans fatty acids in M diet might have counteracted the cholesterol neutral/decreasing effect and increased plasma triacylglycerol.     

Protective effect of oleuropein, an olive oil biophenol, on low density lipoprotein oxidizability in rabbits

On the basis of the results obtained with pilot studies conducted in vitro on human low density lipoprotein (LDL) and on cell cultures (Caco-2), which had indicated the ability of certain molecules present in olive oil to inhibit prooxidative processes, an in vivo study was made of laboratory rabbits fed special diets. Three different diets were prepared: a standard diet for rabbits (diet A), a standard diet for rabbits modified by the addition of 10% (w/w) extra virgin olive oil (diet B), a modified standard diet for rabbits (diet C) differing from diet B only in the addition of 7 mg kg⁻¹ of oleuropein. A series of biochemical parameters was therefore identified, both in the rabbit plasma and the related isolated LDL, before and after Cu-induced oxidation. The following, in particular, were selected: (i) biophenols, vitamins E and C, uric acid, and total, free, and ester cholesterol in the plasma; (ii) proteins, triglycerides, phospholipids, and total, free, and ester cholesterol in the native LDL (for the latter, the dimensions were also measured); (iii) lipid hydroperoxides, aldehydes, conjugated dienes, and relative electrophoretic mobility (REM) in the oxidized LDL (ox-LDL). In an attempt to summarize the results obtained, it can be said that this investigation has not only verified the antioxidant efficacy of extra virgin olive oil biophenols and, in particular, of oleuropein, but has also revealed a series of thus far unknown effects of the latter on the plasmatic lipid situation. In fact, the addition of oleuropein in diet C increased the ability of LDL to resist oxidation (less conjugated diene formation) and, at the same time, reduced the plasmatic levels of total, free, and ester cholesterol (−15, −12, and −17%, respectively), giving rise to a redistribution of the lipidic components of LDL (greater phospholipid and cholesterol amounts) with an indirect effect on their dimesions (bigger by about 12%).     

Rosuvastatin Enhances the Catabolism of LDL apoB‐100 in Subjects with Combined Hyperlipidemia in a Dose Dependent Manner

Dose‐associated effects of rosuvastatin on the metabolism of apolipoprotein (apo) B‐100 in triacylglycerol rich lipoprotein (TRL, d < 1.019 g/ml) and low density lipoprotein (LDL) and of apoA‐I in high density lipoprotein (HDL) were assessed in subjects with combined hyperlipidemia. Our primary hypothesis was that maximal dose rosuvastatin would decrease the apoB‐100 production rate (PR), as well as increase apoB‐100 fractional catabolic rate (FCR). Eight subjects received placebo, rosuvastatin 5 mg/day, and rosuvastatin 40 mg/day for 8 weeks each in sequential order. The kinetics of apoB‐100 in TRL and LDL and apoA‐I in HDL were determined at the end of each phase using stable isotope methodology, gas chromatography‐mass spectrometry, and multicompartmental modeling. Rosuvastatin at 5 and 40 mg/day decreased LDL cholesterol by 44 and 54 % (both P < 0.0001), triacylglycerol by 14 % (ns) and 35 % (P < 0.01), apoB by 30 and 36 % (both P < 0.0001), respectively, and had no significant effects on HDL cholesterol or apoA‐I levels. Significant decreases in plasma markers of cholesterol synthesis and increases in cholesterol absorption markers were observed. Rosuvastatin 5 and 40 mg/day increased TRL apoB‐100 FCR by 36 and 46 % (both ns) and LDL apoB‐100 by 63 and 102 % (both P < 0.05), respectively. HDL apoA‐I PR increased with low dose rosuvastatin (12 %, P < 0.05) but not with maximal dose rosuvastatin. Neither rosuvastatin dose altered apoB‐100 PR or HDL apoA‐I FCR. Our data indicate that maximal dose rosuvastatin treatment in subjects with combined hyperlipidemia resulted in significant increases in the catabolism of LDL apoB‐100, with no significant effects on apoB‐100 production or HDL apoA‐I kinetics.     

Influence of cholesterol feeding and dietary restriction on cholesterol absorption in rabbits

Plasma cholesterol and cholesterol absorption were measured in rabbits given either a standard or cholesterol-rich diet which were fed either ad libitum or reduced to 50% of the control ration. The results confirmed the aggravating effect of dietary restriction on the plama cholesterol response to cholesterol feeding. Hypercholesterolemia was doubled when cholesterol feeding was associated with reduced dietary intake. The percentage of cholesterol absorbed increased significantly in cholesterolfed rabbits on normal caloric ration, while dietary restriction had no effect on this parameter either with the standard or the cholesterol-rich diet. These data indicate that the mechanisms by which plasma cholesterol increases in response to cholesterol feeding involve increased cholesterol absorption. Nevertheless the aggravating effect of dietary restriction cannot be attributed to increased cholesterol absorption.     

Diet,cholesterol metabolism,and atherosclerosis

Effects of diet on acetate incorporation into cholesterol and fatty acids in liver slices, and on the level of plasma cholesterol, were studied in rats and rabbits. Feeding fats and oils in a com-mercial diet stimulated acetate incorporation into rat-liver cholesterol much more than feeding them in a semisynthetic diet. This effect seemed to be specific for cholesterol since incorporation into fatty acids was not similarly affected. High levels of dietary casein inhibited acetate incorporation into both cholesterol and fatty acids. Rat-liver slices generally incorporated more acetate into cholesterol than rabbit-liver slices, but incorpora-tion into fatty acids was often higher in the latter. Rabbit plasma cholesterols were higher on butter diets than on corn oil diets. Further eleva-tion of plasma cholesterol was observed when casein was added to the butter diet but not when it was added to the corn oil diet. Plasma cho-lesterols were elevated, and acetate incorporation into liver cholesterol and fatty acids was inhibited in suckling rats and rabbits whereas recently weaned animals gave results similar to those of adults. The inverse relationship between plasma cholesterol level and acetate incorporation into cholesterol may be attributable to feedback con-trol of liver cholesterol biosynthesis. Other mechanisms which may account for the observed effects of dietary fats and protein on cholesterol metabolism, and the possible relevance of the findings to atherosclerosis, are discussed.     

l-Carnitine effects on chemical composition of plasma lipoproteins of rabbits fed with normal and high cholesterol diets

l-Carnitine plays an important role in the mitochondrial uptake of long-chain fatty acids in mammals. It has recently been shown that this compound has a marked hypo-cholesterolemic effect when used in conjunction with lipid-rich diets. The aim of this study was to investigate the effects of l-carnitine on the fatty acid composition of plasma lipoproteins in rabbits fed with different diets. Four different groups were investigated: group I (standard diet), group II (standard diet supplemented with l-carnitine at 80 mg/kg), group III (standard diet supplemented with 0.5% cholesterol), and group IV (standard diet supplemented with 0.5% cholesterol plus l-carnitine at 80 mg/kg). The feeding period was 126 d. Total plasma cholesterol was indistinguishable in groups I and II, but increased nearly 40-fold in group III. This increment was reduced by 50% in group IV. Correspondingly, total cholesterol content in lipoprotein fractions [very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) separated by agarose gel chromatography was the same for groups I and II, while for animals fed a cholesterol-rich diet (III) total cholesterol in VLDL+LDL increased nearly 100-fold when compared with groups I and II but, again, the increment was reduced by 50% in group IV. In contrast, total cholesterol in HDL increased only fivefold for both groups III and IV when compared with groups I and II, indicating no effects of l-carnitine on this parameter. The reduction of total cholesterol in VLDL+LDL particles in animals fed a cholesterol-rich diet plus l-carnitine was associated with a marked decrease in the ratio of cholesteryl ester to free cholesterol and a dramatic increase in their phospholipid content; opposite effects were observed for HDL. l-Carnitine induced a marked decrease in the saturated to unsaturated C₁₆+C₁₈ fatty acid ratio in cholesteryl esters associated with VLDL and LDL from animals fed with both normal and cholesterol-rich diets. The opposite effect (a large increase in the saturated to unsaturated fatty acid ratio) was observed for both cholesteryl esters and phospholipids associated with HDL in animals fed with both diets. The results suggested that the hypocholesterolemic effects of l-carnitine could be associated with increased systemic breakdown of cholesteryl esters, a probable increase in reverse cholesterol transport, and the stabilization of a phospholipid-based structure of VLDL+LDL particles.     

Mechanisms mediating lipoprotein responses to diets with medium-chain triglyceride and lauric acid

Medium-chain triglycerides (MCT) are often used in specialized formula diets or designer fats because of their special properties. Yet their influence on lipid metabolis is not completely understood. In this two-period cross-over study, the effects of MCT (8∶0+10∶0) in contrast to a similar saturated fatty acid (12∶0) were compared. Eighteen healthy women ate a baseline diet [polyunsaturated (PUFA)/saturated fat=0.9] fer 1 wk. Then, they consumed test diets (PUFA/saturated fat=0.2) for 4 wk. Monounsaturated fat and cholesterol were constant in baseline and treatment diets. MCT and 12∶0, substituted for part of the PUFA, provided 14 energy (en)% of the test diets. In comparison to the PUFA baseline diet, a 16% increase in mean serum low density lipoprotein (LDL)-cholesterol (C) on the 12∶0 diet was accompanied by a 21% decrease in mean receptormediated degradation of LDL by freshly isolated mononuclear cells (MNC) in vitro. The MNC assay theoretically gives an indication of receptor-mediated degradation of LDL. In contrast, the MCT diet raised mean receptor-mediated degradation of LDL by 42%, a finding out of line with the mean 11% increase in serum LDL-C. Perhaps MCT, by increasing the rate of LDL-C production, overcame the rate of LDL-C clearance. The 12∶0 diet enhanced some factors involved in reverse cholesterol transport (e.g., high density lipoprotein fractions) while MCT had a different of less pronounced effect. The overall effects of MCT on cholesterol metabolism may or may not be desirable, whereas those of 12∶0 appear largely undesirable as previously reported.     

Increased HDL Size and Enhanced Apo A-I Catabolic Rates Are Associated With Doxorubicin-Induced Proteinuria in New Zealand White Rabbits

The catabolism and structure of high‐density lipoproteins (HDL) may be the determining factor of their atheroprotective properties. To better understand the role of the kidney in HDL catabolism, here we characterized HDL subclasses and the catabolic rates of apo A‐I in a rabbit model of proteinuria. Proteinuria was induced by intravenous administration of doxorubicin in New Zealand white rabbits (n = 10). HDL size and HDL subclass lipids were assessed by electrophoresis of the isolated lipoproteins. The catabolic rate of HDL‐apo A‐I was evaluated by exogenous radiolabelling with iodine‐131. Doxorubicin induced significant proteinuria after 4 weeks (4.47 ± 0.55 vs. 0.30 ± 0.02 g/L of protein in urine, P < 0.001) associated with increased uremia, creatininemia, and cardiotoxicity. Large HDL2b augmented significantly during proteinuria, whereas small HDL3b and HDL3c decreased compared to basal conditions. HDL2b, HDL2a, and HDL3a subclasses were enriched with triacylglycerols in proteinuric animals as determined by the triacylglycerol‐to‐phospholipid ratio; the cholesterol content in HDL subclasses remained unchanged. The fractional catabolic rate (FCR) of [¹³¹I]‐apo A‐I in the proteinuric rabbits was faster (FCR = 0.036 h^?1) compared to control rabbits group (FCR = 0.026 h^?1, P < 0.05). Apo E increased and apo A‐I decreased in HDL, whereas PON‐1 activity increased in proteinuric rabbits. Proteinuria was associated with an increased number of large HDL2b particles and a decreased number of small HDL3b and 3c. Proteinuria was also connected to an alteration in HDL subclass lipids, apolipoprotein content of HDL, high paraoxonase‐1 activity, and a rise in the fractional catabolic rate of the [¹³¹I]‐apo A‐I.     

Response of plasma lipids to dietary cholesterol and wine polyphenols in rats fed polyunsaturated fat diets

This experiment was designed to evaluate the effects of dietary red wine phenolic compounds (WP) and cholesterol on lipid oxidation and transport in rats. For 5 wk, weanling rats were fed polyunsaturated fat diets (n−6/n−3=6.4) supplemented or not supplemented with either 3 g/kg diet of cholesterol, 5 g/kg diet of WP, or both. The concentrations of triacylglycerols (TAG, P<0.01) and cholesterol (P<0.0002) were reduced in fasting plasma of rats fed cholesterol despite the cholesterol enrichment of very low density lipoprotein + low density lipoprotein (VLDL+LDL). The response was due to the much lower plasma concentration of high density lipoprotein (HDL) (−35%, P<0.0001). In contrast, TAG and cholesteryl ester (CE) accumulated in liver (+120 and +450%, respectively, P<0.0001). However, the cholesterol content of liver microsomes was not affected. Dietary cholesterol altered the distribution of fatty acids mainly by reducing the ratio of arachidonic acid to linoleic acid (P<0.0001) in plasma VLDL+LDL (−35%) and HDL (−42%) and in liver TAG (−42%), CE (−78%), and phospholipids (−28%). Dietary WP had little or no effect on these variables. On the other hand, dietary cholesterol lowered the α-tocopherol concentration in VLDL+LDL (−40%, P<0.003) and in microsomes (−60%, P<0.0001). In contrast, dietary WP increased the concentration in microsomes (+21%, P<0.0001), but had no effect on the concentration in VLDL+LDL. Cholesterol feeding decreased (P<0.006) whereas WP feeding increased (P<0.0001) the resistance of VLDL+LDL to copper-induced oxidation. The production of conjugated dienes after 25 h of oxidation ranged between 650 (WP without cholesterol) and 2,560 (cholesterol without WP) μmol/g VLDL+LDL protein. These findings show that dietary WP were absorbed at sufficient levels to contribute to the protection of polyunsaturated fatty acids in plasma and membranes. They could also reduce the consumption of α-tocopherol and endogenous antioxidants. The responses suggest that, in humans, these substances may be beneficial by reducing the deleterious effects of a dietary overload of cholesterol.     

Oxidative susceptibility of low density lipoprotein from rabbits fed atherogenic diets containing coconut,palm, or soybean oils

The oxidative susceptibilities of low density lipoproteins (LDL) isolated from rabbits fed high-fat atherogenic diets containing coconut, palm, or soybean oils were investigated. New Zealand white rabbits were fed atherogenic semisynthetic diets containing 0.5% cholesterol and either (i) 13% coconut oil and 2% corn oil (CNO), (ii) 15% refined, bleached, and deodorized palm olein (RBDPO), (iii) 15% crude palm olein (CPO), (iv) 15% soybean oil (SO), or (v) 15% refined, bleached, and deodorized palm olein without cholesterol supplementation [RBDPO(wc)], for a period of twelve weeks. Total fatty acid compositions of the plasma and LDL were found to be modulated (but not too drastically) by the nature of the dietary fats. Cholesterol supplementation significantly increased the plasma level of vitamin E and effectively altered the plasma composition of long-chain fatty acids in favor of increasing oleic acid. Oxidative susceptibilities of LDL samples were determined by Cu²⁺-catalyzed oxidation which provide the lag times and lag-phase slopes. The plasma LDL from all palm oil diets [RBDPO, CPO, and RBDPO(wc)] were shown to be equally resistant to the oxidation, and the LDL from SO-fed rabbits were most susceptible, followed by the LDL from the CNO-fed rabbits. These results reflect a relationship between the oxidative susceptibility of LDL due to a combination of the levels of polyun-saturated fatty acids and vitamin E. Based on a paper presented at the PORIM International Palm Oil Congress (PIPOC) held in Kuala Lumpur, Malaysia, 1993.     

Plasma kinetics of a cholesterol-rich emulsion in young, middle-aged, and elderly subjects

Low density lipoprotein (LDL) plasma concentration is increased in the elderly. In this group, the incidence of coronary artery disease (CAD) is greater and LDL remains an important risk factor for CAD development. In this study, the plasma kinetics of a cholesterol-rich emulsion that binds to LDL receptors was studied in 10-subject groups of the elderly (70±4 yr), middle-aged (42±5 yr) and young (23±2 yr). All were normolipidemic, nonobese, nondiabetic subjects who did not have CAD. The emulsion was labeled with ¹⁴C-cholesteryl oleate and injected intravenously into the subjects. Blood samples were drawn at regular intervals over 24 h to determine the plasma decay curve of the emulsion radioactive label and to estimate its plasma fractional clearance rate (FCR, in h⁻¹). FCR of the emulsion label was smaller in elderly compared to young subjects (0.032±0.035 and 0.071±0.049 h⁻¹, respectively; mean±SD, P<0.05). FCR of the middle-aged subjects (0.050±0.071 h⁻¹) was intermediate between the values of the elderly and young subjects, although not statistically different from them. A negative correlation was found between the emulsion FCR and subjects’ age (r=−0.47, P=0.008). We conclude that aging is accompanied by progressively diminished clearance of the emulsion cholesterol esters and, by analogy, of the native LDL.     

Influence of dietary soybean and egg lecithins on lipid responses in cholesterol-fed guinea pigs

The comparative influence on plasma and tissue lipids of dietary soybean and egg lecithins, which have contrasting fatty acid compositions, was studied in the hypercholesterolemic guine apig. The polyunsaturated to saturated fatty acid (P/S) ratios of the soybean and egg lecithins were 3.4 and 0.38, respectively. Hypercholesterolemia was induced by feeding guinea pigs a purified diet that contained 15% lard enriched with 0.5% cholesterol. Subsequently, guinea pigs were fed for six wk the same diet supplemented with either soybean or egg lecithin as 7.5% of the diet. A control group continued to be fed the lecithin-free diet. Parameters measured included body weight and relative liver weight; in plasma, total cholesterol, high density lipoprotein cholesterol (HDLC), phospholipid, and nonesterified cholesterol; in liver, total fat, cholesterol, and the specific activity of the catabolic enzyme cholesterol 7α-hydroxylase; (EC 1.14.13.17); and in the aorta, cholesterol. Among the most noteworthy observations were the 49% decrease in total plasma cholesterol of the soybean lecithin group without decreasing HDLC and the 177% increase in HDLC of the egg lecithin group without a significant increase in total cholesterol compared with those values in the control group. These data suggest that dietary lecithin is particularly effective in increasing the HDLC/total cholesterol ratio in plasma. However, the absolute concentrations of those plasma lipids seem to depend upon the fatty acid composition of the lecithin. Presented in part at the annual meeting of the American Oil Chemists' Society, New Orleans LA, May 1987.     

Cholesterol transport and uptake in miniature swine fed vegetable and animal fats and proteis. 1. Plasma lipoproteins and LDL clearance

In a 2×2 factorial arrangement, miniature pigs were fed four diets containing vegetable protein/fat (soybean) and animal protein (egg white)/fat (beef tallow) to demonstrate the effects of protein and fat source on total plasma cholesterol, lipoprotein distribution, low density lipoprotein (LDL) composition, and plasma clearance of LDL-cholesterol and protein. Beef tallow consumption resulted in greater plasma cholesterol concentration, decreased LDL-cholesterol concentration, and a lower LDL-cholesterol to LDL-protein ratio than did consumption of soybean oil. High density lipoprotein (HDL)-cholesterol concentration was increased by beef tallow consumption. Cholesterol percentage by weight in LDL was significantly greater in pigs consuming soybean oil than those consuming beef tallow. Percentages by weight of protein, triglyceride and phospholipid in LDL were not significantly different in any group. Dietary protein source had no significant effect on total plasma cholesterol concentration, lipoprotein concentration or LDL composition. Egg white consumption decreased fractional catabolic rate and irreversible loss of LDL-cholesterol and LDL-protein when compared with consumption of soy protein. Dietary fat source had no consistent effect on LDL clearance from plasma. Dietary fat and protein seemed to influence lipoprotein metabolism by different mechanisms. Fat source altered lipoprotein concentration and LDL composition, whereas protein source affected the removal rate of LDL from plasma. Data taken from a dissertation submitted to Iowa State University by L. S. Walsh Hentges as partial fulfillment of the requirements for the Ph.D. degree. A preliminary paper, was presented at the meeting of the American Oil Chemists' Society in Dallas, Texas, May, 1984.     

Rat adult offspring serum lipoproteins are altered by maternal consumption of a liquid diet

Palatable liquid diets for the administration of ethanol (EtOH) to animals have proven to be a major advance for the study of the effects of EtOH consumption under conditions of isocaloric nutrition of the control animals. Using a liquid diet, the original aim of the reported studies was to examine the effect of maternal EtOH consumption during pregnancy on the lipoprotein (Lp) profiles of the adult offspring measured by means of nuclear magnetic resonance spectroscopy. However, initial data suggested that compared to a maternal chow diet, the basal maternal liquid diet (without EtOH) had a significant effect on specific serum Lp of the adult offspring. The adult off-spring of mothers who had consumed a basal liquid diet with-out EtOH exhibited significant increases in their plasma triglycerides (TG) and cholesterol content compared to adult offspring whose mothers consumed a chow diet. Further, there were significant increases in the offspring's VLDL and low density Lp (LDL) subfractions' particle number, regardless of whether the maternal liquid diet was ad libitum-fed, pair-fed, or EtOH-containing. The increase in offspring plasma TG was due to increases in specific VLDL subfraction particle numbers and not to increased TG content per particle. Similarly, the increase in plasma cholesterol was the result of elevated level of the very small LDL particles but not to an increased amount of cholesterol per LDL particle. These findings should be further examined in light of the widespread use of liquid diets in, research to administer EtOH, especially for studies of fetal alcohol syndrome.