Hypocholesterolemic effect of anhydrous milk fat ghee is mediated by increasing the secretion of biliary lipids

The anhydrous milk fat ghee is one of the important sources of fat in the Indian diet. Our earlier studies showed that rats fed diets containing greater than 2.5 wt% of ghee had lower levels of serum cholesterol compared with rats fed diets containing groundnut oil. To evaluate the mechanism of the hypocholesterolemic effect of ghee, male Wistar rats were fed a diet containing 2.5 or 5.0 wt% ghee for a period of 8 weeks. The diets were made isocaloric with groundnut oil. Both native and ghee heated at 120 degrees C containing oxidized lipids were included in the diet. The ghee in the diet did not affect the 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity in the liver microsomes, but it significantly increased biliary excretion of cholesterol, bile acids, uronic acid, and phospholipids. The rats fed ghee had lower levels of cholesterol esters in the serum as well as in the intestinal mucosa. Both native and oxidized ghee influenced cholesterol metabolism. These results indicate that supplementation of diets with ghee lipids would increase the excretion of bile constituents and lower serum cholesterol levels.     

The anhydrous milk fat, ghee, lowers serum prostaglandins and secretion of leukotrienes by rat peritoneal macrophages

Ghee, the anhydrous milk fat, is one of the most important sources of dietary fat in India. Male Wistar rats were fed diets containing 2.5, 5.0 and 10 wt% ghee for a period of 8 weeks. The diets were made isocaloric with groundnut oil. The results showed that serum thromboxane levels decreased by 27-35%, and 6-keto-prostaglandin F1alpha by 23-37% when ghee was incorporated at level of 10% in the diet. Prostaglandin E2 levels in serum and secretion of leukotrienes B4, C4 and D4 by peritoneal macrophages activated with calcium ionophore decreased when increased amounts of ghee from 2.5 to 10% were included in the diet. Arachidonic acid levels in macrophage phospholipids decreased when incremental amounts of ghee were fed to rats. These studies indicate that ghee in the diet not only lowers the prostaglandin levels in serum but also decreases the secretion of leukotrienes by macrophages.     

Effect of the ingestion of thermically treated fat on blood lipids and blood lipoproteins in the rat

The effect on rats fed on a diet with 15% solid frying fat (diet B) is compared to the effect of a diet with 15% of the same fat but in the raw state (diet A). After 10 weeks being fed on these diets serum triglycerides, phospholipids, total cholesterol, free cholesterol, esterified cholesterol, high density lipoprotein-cholesterol and free fatty acid levels were checked. Percentage of very low density lipoproteins (VLDL), low density lipoproteins (LDL) and high density lipoproteins as well as the composition of these lipoproteins was determined in parallel. Rats fed on diet B showed a significant increase in phospholipids and a significant decrease in VLDL when compared to those fed on diet A. Phospholipids on LDL decreased significantly in diet B fed rats. The data obtained seem to indicate that the hypercholesterolemic tendency induced by frying fat is neutralized by a decrease in VLDL levels.     

Nutritional evaluation of structured lipid containing omega 6 fatty acid synthesized from coconut oil in rats

Coconut oil is rich in medium chain fatty acids, but deficient in polyunsaturated fatty acids (PUFA). Structured lipids (SL) enriched with omega 6 PUFA were synthesized from coconut oil triglycerides by employing enzymatic acidolysis with free fatty acids obtained from safflower oil. Rats were fed a diet containing coconut oil, coconut oil-safflower oil blend (1:0.7 w/w) or structured lipid at 10% levels for a period of 60 days. The SL lowered serum cholesterol levels by 10.3 and 10.5% respectively in comparison with those fed coconut oil and blended oil. Similarly the liver cholesterol levels were also decreased by 35.9 and 26.6% respectively in animals fed structured lipids when compared to those fed on coconut oil or the blended oil. Most of the decrease observed in serum cholesterol levels of animals fed structured lipids was found in LDL fraction. The triglyceride levels in serum showed a decrease by 17.5 and 17.4% while in the liver it was reduced by 45.8 and 23.5% in the structured lipids fed animals as compared to those fed coconut oil or blended oil respectively. Differential scanning calorimetric studies indicated that structured lipids had lower melting points and solid fat content when compared to coconut oil or blended oils. These studies indicated that enrichment of coconut oil triglycerides with omega 6 fatty acids lowers its solid fat content. The omega 6 PUFA enriched structured lipids also exhibited hypolipidemic activity.     

Effect of long term feeding of rice bran oil upon lipids and lipoproteins in rats

The effects of feeding two levels of rice bran oil (RBO) on the growth, lipid parameters, and fatty acid composition of the plasma and liver of rats (Wistar strain) were compared with those produced on animals which had been fed the same levels of peanut oil (PNO). The control animals were fed synthetic diets containing 5 and 20% peanut oil (PNO) and the experimental groups were fed similar diets, containing the same level of rice bran oil (RBO). There was no significant difference with respect to the organ weights between the control and the experimental groups. In general, groups fed 20% oil gained more weight than groups fed 5% oil. The animals which received rice bran oil in their diet had, in general, comparatively lower levels of cholesterol, triglycerides and phospholipids. On the other hand, animals receiving 20% rice bran oil in their diet, showed an increase of 20% in high density lipoproteins (HDL-C), within 18 weeks (p<0.05), when compared to the animals fed with peanut oil. Similarly, low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) were lower in RBO-fed groups, than in the PNO-fed groups. There was, however, no significant differences in the cholesterol/phospholipid (C/P) ratio of the two groups. Analysis of plasma and of liver fatty acids indicated, in a general way, the type of fat consumed. There were no significant difference in the P/S ratio, nor any in the oleic/linoleic, oleic/stearic, palmitoleic/palmitic, oleic/palmitic, and oleic/palmitoleic ratios. Furthermore, levels of saturated (SAFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids were identical in both the groups. Thus, our results suggest that feeding a high level of rice bran oil (RBO) has no deleterious effect on the growth and blood lipid profile of rats.Abbreviations PNO peanut oil - RBO rice bran oil - HDL-C high density lipoprotein cholesterol - LDL-C low density lipoprotein cholesterol - VLDL-C very low density lipoprotein cholesterol - SAFA saturated fatty acids - MUFA mono-unsaturated fatty acids     

A comparative study of serum lipoproteins in rabbits fed a natural ingredient diet or low-fat, cholesterol-free, semipurified diets containing casein or isolated soy protein

In rabbits fed a cholesterol-free, semipurified diet containing isolated soy protein, the average total serum cholesterol level was similar to that of rabbits fed a natural ingredient (chow) diet. However, the cholesterol and protein levels in very low density (VLDL) and low density lipoproteins (LDL) tended to increase, while the levels in high density lipoproteins (HDL) were reduced to about half of those on the chow diet, with little change in the cholesterol to protein ratio. Substitution of casein for soy protein in the semipurified diet caused a four- to five-fold increase in total serum cholesterol and a doubling of lipoprotein protein, with an increase of 1.4- to 3.0-fold in the cholesterol to protein ratio of the different lipoprotein fractions. Analysis of the apoproteins (apo) of the plasma lipoproteins indicated that apo B, E, and C all tended to increase in the VLDL and LDL of rabbits fed the soy protein diet compared with those fed chow diet. The levels of each of the apoproteins were increased further by substituting casein for soy protein in the semipurified diet. In this case, apo E showed the greatest relative increase (2.7-fold) in VLDL, while apo B and E were increased to a similar extent (about 4-fold) in LDL. Apo C was approximately doubled in each of these fractions. The apo A content in HDL of rabbits fed the semipurified diets was about half that of rabbits fed chow diet. No marked changes were noted in the apo E or C content of HDL. Separation of isoforms of the soluble apoproteins showed variations between individual animals, but these variations seemed largely unrelated to diet. The results of these studies indicate that semipurified diets produce changes in the serum lipoprotein patterns of rabbits that are only partly due to the protein component of these diets.     

Effects of conjugated linoleic acid on body fat accumulation and serum lipids in hamsters fed an atherogenic diet

Conjugated linoleic acid (CLA) refers to a mixture of naturally occurring positional and geometric isomers of linoleic acid that exist in dairy products and meat. The aim of the present work was to study the effects of c-9,t-11 and t-10,c-12 CLA isomers on body fat accumulation and serum lipids in hamsters fed an atherogenic diet. Hamsters were divided in four groups: one group was fed a chow diet (control) and the other three groups were given semi-purified atherogenic diets with 0.5% linoleic acid (LA), c-9,t-11 or t-10,c-12 CLA. Body weight and food intake were measured daily. After 6 weeks, adipose tissues from different anatomical locations and liver were dissected and weighed. Serum glucose, total cholesterol, HDL-c, LDL-c and triacylglycerol levels, as well as total and free cholesterol, triacylglycerol and phospholipid content in liver were determined by enzymatic methods. No differences in either energy intake or final body weight were found. The addition of t-10,c-12 CLA reduced fat accumulation and led to lower serum cholesterol, as compared with LA group. Nevertheless the level remained higher than in the control animals. The reduction in serum cholesterol was limited to LDL-c. This isomer also reduced triacylglycerol content in liver but did not modify serum triacylglycerol level. In summary, the present study demonstrates that t-10,c-12 CLA is the biologically active agent when anti-obesity and hypocholesterolaemic properties of CLA are considered. In contrast, the isomer c-9,t-11 has no effect on lipid metabolism in hamsters.     

Dietary saturated fatty acid content affects lymph lipoproteins: studies in the rat

We examined effects on intestinal absorption of cholesterol and triglycerides and intestinal lipoprotein formation by feeding rats diets in which saturated fatty acids (palmitic plus stearic) comprised 78%, 68%, 48%, or 38% of triglyceride fatty acids. Absorption into lymph of radiolabeled cholesterol was proportional to triglyceride absorption. The rates of absorption of these lipids were related inversely to the % saturated fatty acids fed. The distribution of newly absorbed cholesterol and triglyceride into intestinal lipoproteins differed. With increasing cholesterol absorption more was recovered in very low density lipoproteins in contrast to the appearance preferentially in chylomicrons of larger quantities of fatty acid. Lymph lipid content did not reflect a consistent pattern in relation to the experimental diet fed. The fatty acid composition of triglyceride-rich lymph lipoproteins resembled the diet closely. One-quarter of the intestinal lymph particles from rats fed the highly saturated diets was flattened and polygonal as judged by electron microscopy if cooled to room temperature; whereas with the same diets, particles collected and isolated at 37 degrees C were round. Proportions of A-I and C apolipoproteins in triglyceride-rich intestinal particles varied inversely; apoA-I increased as fat/cholesterol absorption was greater. Diet-induced alterations in plasma lipoproteins and increased circulating triglycerides in this study in rats were unrelated to the variations in intestinal absorption or lymph lipoprotein formation.     

Dietary fat and cholesterol and serum cholesterol in the gerbil

Groups of gerbils were fed purified diets containing either 10 or 20% of safflower, olive, or coconut oil. Each diet was fed without cholesterol and with 0.1 and 0.2% of added cholesterol. The animals were bled after 2, 4, and 8 wk for the determination of the level of serum cholesterol. The major factors affecting the level of serum cholesterol were the kind of dietary oil, the amount of dietary cholesterol, and the length of time the diet was fed. The level of safflower oil had a statistically significant effect but the level of olive or coconut oil had no significant effect. Various other statistically significant interactions were observed which make simple interpretations of the data difficult. The levels of serum cholesterol achieved in the gerbils fed the different oils with no or very low levels of dietary cholesterol were similar to those seen in men fed the same oils. Although the gerbil is apparently resistant to the development of atherosclerosis, it may be a useful model for studying the effect of dietary fats upon cholesterol metabolism.     

Dietary influences on serum lipids and lipoproteins

Substantial data are available to indicate that the diet influences serum levels of cholesterol and lipoproteins. These data are derived from studies in laboratory animals, from epidemiologic studies, and from human investigations. Most research has focused on effects of diet on serum total cholesterol concentrations. In recent years, however, attention has shifted to individual lipoproteins, i.e., low density lipoproteins (LDL), high density lipoproteins (HDL), and very low density lipoproteins (VLDL). Three nutritional factors have been identified that raise serum LDL levels; these are saturated fatty acids, cholesterol itself, and excess caloric intake leading to obesity. The major cholesterol-raising saturated fatty acid in the diet is palmitic acid. Several nutrients can be substituted for saturated fatty acids to produce a reduction in LDL-cholesterol levels. These are polyunsaturated fatty acids, monounsaturated fatty acids, carbohydrates, and even one saturated fatty acid, stearic acid. The latter appears to be converted rapidly into a monounsaturated fatty acid in the body. Any of these nutrients can be used for replacement of cholesterol-raising saturated fatty acids in the diet. However, their relative effects on other metabolic processes remain to be determined fully. At present it appears that carbohydrates and monounsaturated fatty acids represent the preferred replacements for saturated fatty acids, although modest increases in polyunsaturated fatty acids and stearic acid, at the expense of cholesterol-raising saturates, probably are safe and may provide for greater variety in the diet.     

Dietary intervention of cow ghee and soybean oil on expression of cell cycle and apoptosis related genes in normal and carcinogen treated rat mammary gland

The present study investigated the effect of cow ghee (clarified butter fat) versus soybean oil on the expression of cyclins A and D1, and apoptosis regulating Bax, Bcl-2 and PKC-α genes in mammary gland of normal and 7,12-dimethylbenz(a)anthracene (DMBA) treated rats. Two groups of 21 days old female rats were fed for 44 weeks diet containing cow ghee or soybean oil (10%). The animals were given DMBA (30 mg/kg body weight) through oral intubation after 5 weeks feeding. Another two groups fed similarly but not given DMBA served as respective controls. In control groups, the expression of cyclin A was similar on both cow ghee and soybean oil, but that of cyclin D1 was more on soybean oil diet. However, in DMBA treated groups, the expression levels of cyclins A and D1 were significantly greater on soybean oil than on cow ghee. The expression levels of Bax, Bcl-2 and PKC-α were similar in two control groups. However, in tumor tissue expression levels of Bcl-2 and PKC-α were significantly lower in cow ghee fed rats than in soybean oil fed ones, but Bax was similarly expressed in both DMBA treated groups. The pro-apoptotic ratio Bax/Bcl-2 increased and the anti-apoptotic ratio PKC-α*(Bcl-2/Bax) decreased in cow ghee group compared to soybean oil group in DMBA treated rats. Hence, the decreased expressions of cyclins A and D1, Bcl-2 and PKC-α mediate the mechanism by which cow ghee protects from mammary carcinogenesis.     

Studies on the expression of genes encoding apolipoproteins B100 and B48 and the low density lipoprotein receptor in nonhuman primates. Comparison of dietary fat and cholesterol

African green monkeys were fed diets containing low and moderate cholesterol concentrations with either polyunsaturated or unsaturated fat as 40% of calories. Plasma total cholesterol, low density lipoprotein (LDL) cholesterol, and apoB concentrations generally were higher in animals fed (a) the higher dietary cholesterol concentration and (b) saturated fat. At necropsy, liver and intestine were removed, and measurement of mRNAs for LDL receptors (liver) and for apolipoprotein B (liver and intestine) was done. Monkey small intestine mucosa made exclusively apoB48 while the liver made only apoB100, although apoB mRNA in both tissues was the same size (14 kilobases). No dietary cholesterol or fat effects were found for apoB mRNA abundance in the liver, while the animals fed the higher dietary cholesterol level had 50% lower levels of hepatic LDL receptor mRNA. In a separate group of animals, livers were perfused and the rate of apoB secretion was measured. No dietary fat effect on apoB secretion rate was found, and no relationship between plasma LDL cholesterol concentration and the rate of hepatic apoB production existed. These findings support the idea that the dietary factors that increase LDL concentrations act by reducing clearance of apoB-containing particles rather than by increasing production of these lipoproteins. Hepatic LDL receptor mRNA was similar in abundance in polyunsaturated fat and saturated fat-fed animals, suggesting that the difference in plasma cholesterol concentration between these groups is not mediated via effects on LDL receptor mRNA abundance. The level of intestinal apoB mRNA was about 30% higher in animals fed the moderate dietary cholesterol concentration. Earlier studies have shown that more cholesterol is transported in chylomicrons from the intestine when dietary cholesterol levels are higher, and the increased intestinal apoB mRNA abundance may reflect increased intestinal cholesterol transport and chylomicron apoB48 production.     

Influence of dietary trans-fatty acids on swine lipoprotein composition and structure.

Four groups of 20 weanling swine each were fed either (a) basal diet, (b) basal plus hydrogenated fat (13% trans), (c) basal plus hydrogenated fat (13% trans) and 0.4% cholesterol, or (d) basal plus beef tallow (all cis). After six months of feeding, the animals were killed and the blood and aortas were removed. Very low density, low density, and high density lipoproteins were then isolated from the plasma by ultracentrifugal flotation. Although the fatty acid composition of the basal diet was different from the diets supplemented with either hydrogenated fat containing trans-fatty acid or beef tallow containing all cis, the lipid and fatty acid compositions of each of the isolated lipoprotein classes for the four groups of animals were remarkably similar. Elaidate was clearly incorporated into the lipoproteins of animals fed hydrogenated fat, but the level of incorporation was generally less than 5%. In a direct comparison of the structure of the lipoproteins from the different groups, we did not find any significant differences in their physical properties as determined by pyrene fluorescence and electron paramagnetic resonance methods. Grossly visible fatty streaks and fibrous plaques were not found in any of the swine aorta. However, light and electron microscopy indicated the presence of atherosclerotic lesions in the distal abdominal aorta and bifurcation. These studies demonstrate that a diet containing a substantial amount of trans-fatty acid leads to a small but definite incorporation into the swine lipoproteins. However, such changes had relatively little effect on lipoprotein structure or the presence of atherosclerotic lesions in these 6-month-old swine.     

Monounsaturated fatty acyl-coenzyme A is predictive of atherosclerosis in human apoB-100 transgenic, LDLr-/- mice

ACAT2, the enzyme responsible for the formation of cholesteryl esters incorporated into apolipoprotein B-containing lipoproteins by the small intestine and liver, forms predominantly cholesteryl oleate from acyl-CoA and free cholesterol. The accumulation of cholesteryl oleate in plasma lipoproteins has been found to be predictive of atherosclerosis. Accordingly, a method was developed in which fatty acyl-CoA subspecies could be extracted from mouse liver and quantified. Analyses were performed on liver tissue from mice fed one of four diets enriched with one particular type of dietary fatty acid: saturated, monounsaturated, n-3 polyunsaturated, or n-6 polyunsaturated. We found that the hepatic fatty acyl-CoA pools reflected the fatty acid composition of the diet fed. The highest percentage of fatty acyl-CoAs across all diet groups was in monoacyl-CoAs, and values were 36% and 46% for the n-3 and n-6 polyunsaturated diet groups and 55% and 62% in the saturated and monounsaturated diet groups, respectively. The percentage of hepatic acyl-CoA as oleoyl-CoA was also highly correlated to liver cholesteryl ester, plasma cholesterol, LDL molecular weight, and atherosclerosis extent. These data suggest that replacing monounsaturated with polyunsaturated fat can benefit coronary heart disease by reducing the availability of oleoyl-CoA in the substrate pool of hepatic ACAT2, thereby reducing cholesteryl oleate secretion and accumulation in plasma lipoproteins.     

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.     

Influence of neonatal age on changes in fatty acid composition of microsomal lipids induced by long-term and short-term cholesterol feeding

Changes observed as a function of chick age in fatty acid composition of lipids from liver microsomes were considerably small, while the unsaturation index increased throughout postnatal development. Supplementation of the diet with 2% cholesterol from hatching produced a significant decrease in the levels of palmitic acid and a clear increase in those of polyunsaturated fatty acids. Maximum effects were attained on day 19 of treatment. Alterations in the fatty acid composition were more pronounced after short-term (48 h) cholesterol feeding. Administration for 48 h of a standard diet to chicks fed a cholesterol diet for 10 days from hatching restored the levels of fatty acids to those of the controls. However, when cholesterol feeding was prolonged for 24 days from hatching, no effect was found after the same treatment. Suppression of the cholesterol diet for 48 h in animals cholesterol fed for 48 h had no effect in 12-day-old chicks while the change to a standard diet produced a reversion of the effect of cholesterol feeding in 26-day-old animals.     

Zinc deficiency and the activities of lipoprotein lipase in plasma and tissues of rats force-fed diets with coconut oil or fish oil

The present study was performed to investigate the effect of zinc deficiency on the activities of lipoprotein lipase in postheparin serum and tissues of rats fed diets containing either coconut oil or fish oil as dietary fat, using a bifactorial experimental design. To ensure an adequate food intake, all the rats were force-fed by gastric tube. Experimental diets contained either 0.8 mg zinc/kg (zinc-deficient diets) or 40 mg zinc/kg (zinc-adequate diets). The effects of zinc deficiency on the activities of lipoprotein lipase in postheparin serum and postprandial triglyceride concentrations and distribution of apolipoproteins in serum lipoproteins depended on the type of dietary fat. Zinc-deficient rats fed the coconut oil diet exhibited a reduced activity of lipoprotein lipase in postheparin serum and adipose tissue, markedly increased concentrations of triglycerides in serum, and a markedly reduced content of apolipoprotein C in triglyceride-rich lipoproteins and high density lipoproteins compared with zinc-adequate rats fed coconut oil. By contrast, zinc-deficient rats fed the fish oil diet did not exhibit reduced activities of lipoprotein lipase in postheparin serum and adipose tissue and increased concentrations of serum lipids compared with zinc-adequate rats fed the fish oil diet. This study suggests that a reduced activity of lipoprotein lipase might contribute to increased postprandial concentrations of serum triglycerides observed in zinc-deficient animals. However, it also demonstrates that the effects of zinc deficiency on lipoprotein metabolism are influenced by dietary fatty acids.     

A Murine Model of Obesity With Accelerated Atherosclerosis

The epidemic of obesity sweeping developed nations is accompanied by an increase in atherosclerotic cardiovascular diseases. Dyslipidemia, diabetes, hypertension, and obesity are risk factors for cardiovascular disease. However, delineating the mechanism of obesity‐accelerated atherosclerosis has been hampered by a paucity of animal models. Similar to humans, apolipoprotein E–deficient (apoE^?/?) mice spontaneously develop atherosclerosis over their lifetime. To determine whether apoE^?/? mice would develop obesity with accelerated atherosclerosis, we fed mice diets containing 10 (low fat (LF)) or 60 (high fat (HF)) kcal % from fat for 17 weeks. Mice fed the HF diet had a marked increase in body weight and atherosclerotic lesion formation compared to mice fed the LF diet. There were no significant differences between groups in serum total cholesterol, triglycerides, or leptin concentrations. Plasma concentrations of the acute‐phase reactant serum amyloid A (SAA) are elevated in both obesity and cardiovascular disease. Accordingly, plasma SAA concentrations were increased fourfold (P < 0.01) in mice fed the HF diet. SAA was associated with both pro‐ and antiatherogenic lipoproteins in mice fed the HF diet compared to those fed the LF diet, in which SAA was primarily associated with the antiatherogenic lipoprotein high‐density lipoprotein (HDL). Moreover, SAA was localized with apoB‐containing lipoproteins and biglycan in the vascular wall. Taken together, these data suggest male apoE‐deficient mice are a model of metabolic syndrome and that chronic low level inflammation associated with increased SAA concentrations may mediate atherosclerotic lesion formation.     

Dietary fat saturation and gender/hormonal status modulate plasma lipids and lipoprotein composition(1)

Male, female and ovariectomized (to mimic menopause) guinea pigs were fed a saturated (SFA) or a polyunsaturated (PUFA) fat diet for 4 weeks to determine the effects of dietary fat saturation on lipoprotein levels and composition and to assess whether gender and hormonal status modulate the cholesterolemic response. Both diets contained 15g/100 g fat and 0.04 g/100 g cholesterol and were identical in composition except for the type of fat. The SFA diet contained 50% saturated fat (25% lauric + myristic fatty acids), 25% PUFA and 25% monounsaturated fatty acids while the PUFA diet had 50% PUFA (linoleic acid), 25% monounsaturated and 25% SFA fatty acids. Plasma LDL cholesterol (LDL-C) was an average 21% lower in guinea pigs fed PUFA compared to those fed SFA (P < 0.05). In addition, ovariectomized guinea pigs, both in the SFA and PUFA groups, had 20–33% higher LDL-C than either males or females (P < 0.01). VLDL cholesterol was 70% higher in the PUFA-fed animals (P < 0.0001). A gender effect was observed in plasma HDL cholesterol (HDL-C) with females and ovariectomized guinea pigs having 30–42% higher HDL-C than males (P < 0.01). LDL susceptibility to oxidation was not affected by dietary fat saturation or gender. In contrast, VLDL and LDL composition were significantly influenced by diet and gender. VLDL particles were larger in size in guinea pigs fed the SFA diets (P < 0.01) while LDL particles were larger in female guinea pigs (P < 0.001). Hepatic lipids were influenced by the interaction between diet and group. Hepatic cholesterol (P < 0.01) and TAG concentrations (P < 0.0001) were highest in female guinea pigs fed the PUFA diet. Since the liver is the major site of lipoprotein synthesis and catabolism, these results suggest that not only diet but also gender may play a major role in determining the composition and size of lipoproteins.