Dietary fat saturation affects apolipoprotein AII levels and HDL composition in postmenopausal women.

Increased HDL-cholesterol levels have been associated with lower coronary heart disease (CHD) risk. However, HDL are heterogeneous lipoproteins, and particles enriched in apolipoprotein (Apo) AII have been associated with increased CHD risk. We examined the effect of dietary intervention on HDL composition in 14 postmenopausal women subjected to two consecutive diet periods, i.e., an oleic acid sunflower oil diet followed by a palmolein diet, each lasting 4 wk. The linoleic acid was kept at 4% total energy and the cholesterol intake at 400 mg/d. The palmolein diet increased serum total cholesterol (TC) (P < 0.001), phospholipids (P < 0.001), Apo AII (P < 0.001), HDL cholesterol (P < 0.05), HDL lipids (P < 0.05), HDL proteins (P < 0.01) and the HDL total mass (P < 0.05). The HDL cholesterol/Apo AI ratio was increased 22.0% (P < 0.05), whereas the HDL cholesterol/Apo AII and the Apo AI/Apo AII ratios were decreased 19.4% (P < 0.01) and 30.4%, (P < 0.001), respectively. When the effects of the dietary intervention were examined according to the cholesterolemia status (< or >6.2 mmol/L), the most significant changes (P < 0.001) were related to Apo AII levels. Moreover, a significant dietary oil by cholesterol level interaction was found for Apo AII and the HDL cholesterol/Apo AII ratio. In summary, a palmolein diet increased TC and HDL cholesterol compared with oleic acid sunflower oil diet; however, the increase in Apo AII but not in Apo AI suggests the impairment of reverse cholesterol transport and potentially an increase in CHD risk. This effect was more marked in women with serum TC > 6.2 mmol/L.     

Dietary fat type affects vitamins C and E and biomarkers of oxidative status in peripheral and brain tissues of golden Syrian hamsters

Oxidative stress is an important trigger in the complex chain of events leading to neurodegenerative diseases. On the other hand, dietary fatty acids play an essential role in brain function. The objectives of this study were to assess the effect of dietary fat type on vitamin C and vitamin E (alpha-and gamma-tocopherol) concentrations in peripheral and brain tissues and its effect on 8-epiPGF(2)alpha (F(2)-isoprostanes). Male Golden Syrian hamsters (n = 120, 8 wk old) were fed diets enriched in butter, hydrogenated fat (margarine), and canola and soybean oils. After 12 wk, hamsters were deprived of food, anesthetized with isoflurane, and killed via terminal exsanguination. Analyses of vitamins C, E, and 8-epiPGF(2)alpha were performed in peripheral tissues and brain. Hamsters consuming the margarine-enriched diet had lower (P < 0.05) vitamin C and alpha-tocopherol concentrations in liver, plasma, and brain, and higher (P < 0.02) plasma 8-epiPGF(2)alpha than groups fed the butter, and the canola and soybean oil diets. Liver and plasma gamma-tocopherol concentration was higher (P < 0.001) among the groups fed the soybean- and margarine-enriched diets compared with the other groups. alpha-Tocopherol was higher (P < 0.05) and 8-epiPGF(2)alpha lower (P < 0.01) among the groups fed the canola and soybean oil diets compared with the other groups. Across the groups, an inverse correlation between plasma levels of vitamin C and 8-epiPGF(2)alpha (r = -0.37, P = 0.03) and a positive correlation between plasma levels of vitamin C and alpha-tocopherol were observed (r = 0.341, P = 0.003). Hamsters fed the butter-enriched diet had a higher (P < 0.03) plasma uric acid concentration than the other groups. The results of this study provide new evidence concerning the effect of dietary fat on antioxidant status, which is important for the maintenance of good health.     

Dietary fat and cholesterol modulate the plasma lipoprotein distribution and production of pigment or cholesterol gallstones in hamsters.

To evaluate the impact of key dietary factors on plasma lipoproteins and gallstone induction, male Syrian hamsters were fed either cholesterol and fat-supplemented purified diets containing glucose or lactose, or cholesterol and fat-free diets with or without fiber, for 13 wk. Fat-supplemented hamsters were hyperlipidemic in comparison to those fed fat-free diets. The former group revealed a greatly expanded VLDL fraction, whereas a normal HDL2 pool predominated in the latter group. Plasma fatty acids indicated that hamsters fed the fat-free diet were essential fatty acid deficient whilst the hamsters fed the fat-supplemented diet were subnormal in essential fatty acids. Ninety-three percent of the hamsters fed the fat-supplemented diet had gallstones (mostly cholesterol), whereas 62% of hamsters fed the fat-free diet had gallstones (almost all pigmented). Lactose increased cecal weight and prevented pigment stone formation in the fat-supplemented hamsters, whereas adding fiber to the fat-free diet contributed essential fatty acids, eliminated cholesterol stones and enhanced pigment stone formation. Thus, diets containing casein, rice flour, glucose and fiber with minimal essential fatty acids but no cholesterol promoted pigment stones (associated with a normal lipoprotein profile); a low fat diet limited in essential fatty acids but containing cholesterol and lactose, promoted cholesterol gallstones (associated with an expanded VLDL pool).     

Dietary fat saturation affects hepatocyte insulin binding and glucose metabolism in BHE rats

The influence of feeding 6% hydrogenated coconut oil, corn oil or menhaden oil on hepatocyte insulin binding, receptor number and glucose use was studied. Hepatocytes isolated from rats fed menhaden oil had a significantly greater affinity for insulin than hepatocytes from rats fed hydrogenated coconut oil. Glucose use was not influenced by diet; uniformly labeled glucose was metabolized to CO2 or to lipid similarly in cells isolated from rats fed the three oils. Thus, dietary fat type in a low fat diet influenced events at the plasma membrane without influencing intracellular events.     

Study of diet-induced changes in lipoprotein metabolism in two strains of Golden-Syrian hamsters

The objective of this study was to characterize two strains of Golden-Syrian hamsters for use in the study of diet-induced changes in lipoprotein metabolism. In Experiment 1, the time course and response to dietary saturated fat was investigated for serum lipoprotein profiles and aortic lesion formation in Golden-Syrian hamsters from Charles River Laboratories, Wilmington, MA (CR) and Bio Breeders, Watertown, MA (F(1)B). Hamsters were fed a nonpurified diet containing 10 g/100 g saturated fat and 0.1 g/100 g dietary cholesterol. After 12 wk, CR hamsters had significantly lower serum total and non-HDL cholesterol (TC and nHDL-C) levels, but higher aortic cholesteryl ester (CE) than the F(1)B hamsters (P < 0.05). In Experiment 2, CR hamsters were fed a nonpurified diet containing 10 g/100 g saturated fat and 0.1, 0.5 or 1 g/100 g dietary cholesterol. After 10 wk of dietary intervention, TC and nHDL-C levels were significantly higher in the 0.5 and 1.0 g/100 g cholesterol groups than in the 0.1 g/100 g cholesterol group. These levels declined after 20 wk of dietary intervention in all groups, potentially reflecting the toxic effect of high cholesterol intakes. CR hamsters fed a 10 g/100 g saturated fat containing 0.1 g/100 g dietary cholesterol for 10 wk appear to be a good model for investigating diet-induced change in plasma lipids.     

Dietary fish protein modulates high density lipoprotein cholesterol and lipoprotein lipase activity in rabbits.

To explore the pathways by which fish protein feeding influences HDL metabolism, postheparin plasma lipoprotein lipase and hepatic triglyceride lipase activities were measured in rabbits fed fish protein or soybean protein combined with corn oil or coconut oil in a 2 x 2 factorial arrangement. In addition to greater serum total and LDL-cholesterol concentrations, the elevated HDL cholesterol concentration caused by feeding fish protein, compared with soybean protein, was accompanied by lower VLDL triglycerides and parallel higher lipoprotein lipase activity in fish protein-fed rabbits. These results suggest an enhanced assembly of circulating HDL through promoted lipoprotein lipase activity in rabbits fed fish protein. Moreover, dietary proteins and lipids interacted with one another to alter HDL triglycerides and liver cholesterol concentrations. Diet-induced changes in lipoprotein lipase activity were, however, not related to insulinemia, which was unaltered by purified diet feeding. The present results suggest that fish protein may affect HDL metabolism through the modulation of lipoprotein lipase activity in rabbits.     

Low fat and high monounsaturated fat diets decrease human low density lipoprotein oxidative susceptibility in vitro

Oxidative modification of low density lipoprotein (LDL) is thought to play an important role in the development of atherosclerosis. Some studies have found that LDL enriched in monounsaturated fatty acids (MUFA) are less susceptible to oxidation than LDL enriched in polyunsaturated fatty acids (PUFA). A high MUFA diet is an alternative to a lower-fat blood cholesterol-lowering diet. Less is known about the effects of high MUFA versus lower-fat blood cholesterol-lowering diets on LDL oxidative susceptibility. The present study was designed to evaluate the effects of men and women consuming diets high in MUFA (peanuts plus peanut butter, peanut oil and olive oil) on LDL oxidative susceptibility, and to compare these effects with those of a Step II blood cholesterol-lowering diet. A randomized, double-blind, five-period crossover design (n = 20) was used to study the effects of the following diets on LDL-oxidation: average American [35% fat, 15% saturated fatty acids (SFA)], Step II (25% fat, 7% SFA), olive oil (35% fat, 7% SFA), peanut oil (35% fat, 7% SFA) and peanuts plus peanut butter (35% fat, 8% SFA). The average American diet resulted in the shortest lag time (57 +/- 6 min) for LDL oxidized ex vivo, whereas the Step II, olive oil and peanuts plus peanut butter diets resulted in a lag time of 66 +/- 6 min (P < or = 0.1). The slower rate of oxidation [nmol dienes/(min x mg LDL protein)] observed when subjects consumed the olive oil diet (24 +/- 2) versus the average American (28 +/- 2), peanut oil (28 +/- 2) and peanuts plus peanut butter diets (29 +/- 2; P < or = 0.05) was associated with a lower LDL PUFA content. The results of this study suggest that lower-fat and higher-fat blood cholesterol-lowering diets high in MUFA have similar effects on LDL oxidative resistance. In addition, our results suggest that different high MUFA sources varying in the ratio of MUFA to PUFA can be incorporated into a high MUFA diet without increasing the susceptibility of LDL to oxidation.     

Algal docosahexaenoic acid affects plasma lipoprotein particle size distribution in overweight and obese adults

Fish oils containing both EPA and DHA have been shown to have beneficial cardiovascular effects, but less is known about the independent effects of DHA. This study was designed to examine the effects of DHA on plasma lipid and lipoprotein concentrations and other biomarkers of cardiovascular risk in the absence of weight loss. In this randomized, controlled, double-blind trial, 36 overweight or obese adults were treated with 2 g/d of algal DHA or placebo for 4.5 mo. Markers of cardiovascular risk were assessed before and after treatment. In the DHA-supplemented group, the decrease in mean VLDL particle size (P ≤ 0.001) and increases in mean LDL (P ≤ 0.001) and HDL (P ≤ 0.001) particle sizes were significantly greater than changes in the placebo group. DHA supplementation also increased the concentrations of large LDL (P ≤ 0.001) and large HDL particles (P = 0.001) and decreased the concentrations of small LDL (P = 0.009) and medium HDL particles (P = 0.001). As calculated using NMR-derived data, DHA supplementation reduced VLDL TG (P = 0.009) and total TG concentrations (P = 0.006). Plasma IL-10 increased with DHA supplementation to a greater extent than placebo (P = 0.021), but no other significant changes were observed in glucose metabolism, insulin sensitivity, blood pressure, or markers of inflammation with DHA. In summary, DHA supplementation resulted in potentially beneficial changes in some markers of cardiometabolic risk, whereas other markers were unchanged.     

Dietary fat saturation affects glucose metabolism without affecting insulin receptor number and affinity in adipocytes from BHE rats

The effects of dietary fat source on epididymal fat cell insulin receptor binding and affinity and on glucose transport and use by genetically diabetic rats were studied. Male BHE rats were fed 6% fat/64% sucrose diets. The fat consisted of 1% corn oil plus 5% beef tallow, menhaden oil or corn oil. Glucose tolerance was assessed at 100, 300 and 600 d of age. At 100 d of age the fat pads were excised, isolated adipocytes prepared and insulin receptor number, receptor affinity, 3-O-methyl glucose uptake and glucose use determined. Insulin receptor number and binding affinity were not affected by dietary fat type. The transport and subsequent use of glucose were greater in fat cells from rats fed beef tallow compared with those from rats fed corn oil or menhaden oil. All three groups exhibited a deterioration in glucose tolerance with age. Although we observed greater glucose transport, oxidation and conversion to fatty acids in beef tallow-fed rats, we saw no differences in these measurements between cells from corn or menhaden oil-fed rats. Thus, we conclude that the effects of these dietary lipids are attributable to effects of saturated fatty acids on intracellular events rather than on the insulin receptor per se, and that the type of unsaturated fatty acid [(n-3) vs. (n-6)] is of little importance to the regulation of glucose metabolism by isolated adipocytes.     

高锌摄人对机体血脂 脂蛋白及载脂蛋白代谢的影响

目的：观察健康人高锌摄入对血脂、脂蛋白及栽脂蛋白代谢的影响，为合理用锌提供依据。方法：选择长清县五峰乡当地居民38例，服葡萄糖酸锌(0.2g，含锌50mg／d)，每次专人送药，连服8周。在服药前、服药后4、8周3次查体，描记心电图，测定血压。3次查体同时取静脉血，测定胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL—C)、高密度脂蛋白胆固醇(HDL—C)、载脂蛋白AI(apoA1)、载脂蛋白B100(apoB100))含量，观察动态变化。结果：服锌4周时TC升高，8周持续升高，TG4周时升高，8周时处稳定状态，8周时LDL—C升高，4周时apoB100升高，8周时apoA1降低，apoA1／apoB100值变小。结论：健康人摄入锌50mg／d时，引起脂类代谢紊乱，临床应谨慎使用锌制剂。     

高锌摄入对机体血脂脂蛋白及载脂蛋白代谢的影响

目的 :观察健康人高锌摄入对血脂、脂蛋白及载脂蛋白代谢的影响 ,为合理用锌提供依据。方法 :选择长清县五峰乡当地居民 38例 ,服葡萄糖酸锌 (0 .2 g ,含锌 5 0mg/d) ,每次专人送药 ,连服 8周。在服药前、服药后 4、8周 3次查体 ,描记心电图 ,测定血压。 3次查体同时取静脉血 ,测定胆固醇 (TC)、甘油三酯 (TG)、低密度脂蛋白胆固醇 (LDL -C)、高密度脂蛋白胆固醇 (HDL -C)、载脂蛋白AI(apoA1)、载脂蛋白B10 0(apoB10 0 ) )含量 ,观察动态变化。结果 :服锌 4周时TC升高 ,8周持续升高 ,TG 4周时升高 ,8周时处稳定状态 ,8周时LDL -C升高 ,4周时apoB10 0升高 ,8周时apoA1降低 ,apoA1/apoB10 0值变小。结论 :健康人摄入锌 5 0mg/d时 ,引起脂类代谢紊乱 ,临床应谨慎使用锌制剂。     

Effect of total parenteral nutrition with intravenous fat on lipids and high density lipoprotein heterogeneity in neonates

Plasma lipid concentrations and high density lipoprotein (HDL) subclass distributions were evaluated in 22 newborn infants nourished with intravenous (iv)-fat. The majority of infants were premature with respiratory distress syndrome. Based on baseline (prior to iv-fat) HDL subclass profiles determined by gradient gel electrophoresis (GGE), infants fell into two classes, one with two or more pronounced peaks within the normal HDL spectrum (group I, 17 subjects) and the other with highly unusual HDL distribution (group II, five subjects). Total plasma cholesterol increased in both groups during low and high fat intravenous feeding. HDL-cholesterol, however, did not change with iv-fat where mean values for groups I and II at baseline, iv-low fat and -high fat were: group I, 31.2 +/- 7.1, 30.0 +/- 8.8, and 36.6 +/- 16.7 mg/dl, respectively; and group II, 20.0 +/- 7.8, 20.2 +/- 7.4, and 19.8 +/- 8.8 mg/dl, respectively. Unlike HDL-cholesterol levels that remained constant with iv-fat, apolipoprotein (apo) AI concentrations increased significantly: group I, 73.0 +/- 11.0, 88.3 +/- 15.9, and 93.1 +/- 21.9 mg/dl, respectively; and group II, 31.8 +/- 10.5, 41.0 +/- 12.8, and 59.3 +/- 18.5 mg/dl, respectively. In group I infants, iv-fat is associated with an increase in larger-sized particles, particularly in the (HDL2b)gge range; in group II there is an increase in (HDL3b)gge and (HDL3c)gge components and a disappearance of particles that fall outside of the size range of normal HDL. In both groups, enteral feeding is associated with a further normalization of HDL subclass distribution. The aberrant GGE profiles and very low apoAI levels of group II infants at baseline were associated with unusual HDL morphology determined by electron microscopy where discoidal structures were prominent. With iv-fat, discoidal particles decline in number while normal spherical structures increase. Prevalence of discoidal HDL at baseline was associated with low concentrations of lecithin:cholesterol acyltransferase (LCAT) (1.12 +/- 0.5 micrograms/ml); with iv-fat this enzyme rose to 1.61 +/- 0.18 micrograms/ml. Increased LCAT is associated with the normalization of HDL morphology. It is likely that iv-fat improves the nutritional status of premature infants, thereby stimulating increased liver synthesis of important proteins, including apoAI and LCAT, associated with HDL metabolism.     

New MspI polymorphism at +83 bp of the human apolipoprotein al gene: Association with increased circulating high density lipoprotein cholesterol levels

We recently showed that loss of a MspI restriction site in the 5′-end (intron 1) of the apolipoprotein (apo) AI gene is due to a C to T transition (+83 bp) and/or a G to A transition (+84 bp). Since this region may be relevant to the regulation of apo AI gene expression and therefore to plasma high density lipoprotein cholesterol (HDL-C), we explored the association between this MspI polymorphic site and circulating HDL-C levels in 243 healthy Caucasians. There were 143 aged 18–67 years (60 males and 83 females) and 100 aged 6–12 years (58 males and 42 females). We also compared this association with a known MspI polymorphic site, a G to A transition at −75 bp of the apo AI gene. The rare allele (−) frequency for the polymorphism at +83 bp was 4.1% and 22.1% for the polymorphism at −75 bp. Subjects heterozygous for the loss of the MspI restriction site at +83 bp (genotype: M2+−, n = 20) had higher HDL-C levels than M2++ subjects (mean ± SD: 1.73 ± 0.31 vs. 1.41 ± 0.39 mmol/l, P < 0.05 for adults; 1.71 ± 0.33 vs. 1.34 ± 0.29 mmol/l, P < 0.01 for children). Adults with the G to A substitution at −75 bp also had higher HDL-C levels (1.56 ± 0.36 mmol/l for AA, 1.53 ± 0.38 mmol/l for GA, and 1.36 ± 0.38 mmol/l for GG, P < 0.05); this difference was not observed in the children. The MspI polymorphisms at both sites were in linkage disequilibrium. Their joint effect on the HDL-C levels was also significant and individuals with rare alleles (−) at both sites had the highest HDL-C levels. In an analysis of variance, the MspI polymorphism at +83 bp, and at −75 bp and gender independently accounted for 6.5%, 1.7%, and 5.9%, respectively, of the variance in circulating HDL-C levels when age was controlled as a covariate. We conclude that loss of the MspI site by the C to T (+83 bp) and/or the G to A (+84 bp) transitions is highly associated with increased HDL-C levels. The association appears to be more significant than that of the G to A transition at −75 bp. © 1996 Wiley-Liss, Inc.     

Plasma lipoprotein profile in fasted and refed chickens of two strains selected for high or low adiposity

The plasma lipoprotein profile has been determined in fasted and refed 5-week-old male broilers selected for low or high adiposity. Lipoprotein classes were subfractionated by density gradient ultracentrifugation, appearing as distinct bands with the following densities: very low density lipoprotein (VLDL), d less than 1.013 g/ml; low density lipoprotein (LDL), d 1.023-1.046 g/ml and high density lipoprotein (HDL), d 1.052-1.130 g/ml; the physiochemical characteristics (chemical composition, electrophoretic mobility and particle size) of these particles were then assessed. HDL, seen as a single band, represented 80% of total lipoproteins, with VLDL and LDL accounting for 1% and 16%, respectively, in fasted birds. Lipoprotein profiles were similar in fasted and refed animals of both lines, with the exception that VLDL levels were some 14-fold and 7-fold higher in the lean and fat lines, respectively, in the refed state. The VLDL of fasted birds of both lines were enriched in protein and relatively homogeneous in size; by contrast, VLDL in the refed state contained more triglyceride and less cholesteryl ester and protein and were larger and more heterogeneous, possibly representing a mixture of portomicrons and VLDL of hepatic origin. Birds of the fat line in both nutritional states differed from lean birds in exhibiting elevated plasma lipid and lipoprotein [VLDL, intermediate density lipoprotein (IDL) and HDL] levels, evidence that liver activity is directed toward increased lipoprotein production and secretion in that line.     

Growth, lipid metabolism and pathology of two strains of rats fed high fat diets.

Studies were carried out on Sprague-Dawley (SD) and Chester Beatty (CB) rats to determine whether the difference in incidence of myocardial lesions can be related to dietary factors and parameters known to be affected in SD rats fed rapeseed oils. The two strains of young, male rats were fed diets which contained 20% by weight of either corn, LEAR (low erucic acid) or HEAR (high erucic acid rapeseed) oils for a period of up to 16 weeks. A significantly lower incidence of focal myocardial necrosis was observed in CB rats than in SD rats. The incidence of this heart lesion in CB rats was similar between all diets; in SD rats a higher incidence was observed in the groups fed rapeseed oils. In both strains the growth rates of rats fed LEAR and corn oils were similar; growth rates with HEAR oil diets were much lower than the other oils. Severe myocardial lipidosis was only evident in rats fed HEAR oil, but no strain differences were observed. The pattern and extent of lipidosis, including cardiac and hepatic lipid levels and fatty acid compositions, were similar in both strains at the time periods studied. Cardiac triglycerides and free fatty acids increased in rats fed HEAR oil, but no strain differences were evident. Strain differences were found in the levels of a few cardiac phospholipids of rats fed HEAR oil, however, the relative fatty acid compositions of each phospholipid were remarkably similar. Microscopic examination of the livers showed no evidence that feeding rapeseed oil caused any specific effect which could be related to differences in heart lesion response. There was no evidence to indicate that differences in heart lesion response between the two rat strains could be related to cardiac triglycerides, free fatty acids or phospholipids.     

Dietary fat source regulates ob gene expression in white adipose tissue of rats under hyperphagic feeding

This work was designed to investigate the effect of different lipid sources on ob gene expression and serum leptin levels in rats with two different feeding protocols: (1) free access to food; or (2) energy-controlled feeding. Male Wistar rats were fed diets containing 40 % energy as fat (olive oil, sunflower oil or beef tallow), for 4 weeks. In Expt 1 rats had free access to food, and in Expt 2 rats were fed a controlled amount of food (16 g/d, equivalent to 300 kJ/d). Insulin and leptin were determined by ELISA and ob mRNA by Northern blot. When rats had free access to food, ob mRNA levels were higher in animals fed either olive oil or sunflower oil than in those fed beef tallow. In marked contrast with feeding ad libitum, no differences were found among dietary fat groups in rats fed energy-controlled diets. When both feeding protocols were compared, free access to food induced an increased expression of ob mRNA in perirenal and/or epididymal adipose tissues from rats fed either olive oil or sunflower oil, but not from rats fed beef tallow. Dietary lipid type did not induce modifications in serum leptin concentrations. A tendency to higher serum leptin levels was observed more in rats with free access to food than in rats fed energy-controlled feeding. No differences were found in insulin levels. Dietary fat type importantly affects ob mRNA expression in rat white adipose tissue under hyperphagic conditions. Further study is needed in order to elucidate the mechanism underlying this effect.     

Determinants of high density lipoprotein and total cholesterol in women.

An epidemiological study was carried out among a random sample of women aged 18 to 69 years to examine possible determinants of plasma high density lipoprotein and total cholesterol (HDL-C and T-C). In a multiple regression analysis consumption of alcohol, fatty fish, and parental longevity showed positive associations with HDL-C, which were statistically significant. Smoking habit, sucrose consumption, and a family history of ischaemic heart disease showed significantly negative associations. In contrast, T-C was associated significantly only with age and Quetelet's index of body mass. Five variables having significant associations with HDL-C explained only 8% of the total variance; in the case of T-C 17% of the variance was explained by age and body mass.