Dependence of the effects of dietary cholesterol and experimental conditions on serum lipids in man. I. Effects of dietary cholesterol in a linoleic acid-rich diet.

In this experiment the effect of dietary cholesterol in a linoleic acid-rich diet on serum cholesterol was tested. In a cross-over design 41 young healthy students received a linoleic acid-rich diet for 4 weeks at two levels of dietary cholesterol. The diet contained 14 to 15 energy% linoleic acid. The high cholesterol diet was obtained by adding two egg yolks a day to the rations. Supplementation of the linoleic acid-rich diet with the egg yolk cholesterol caused a significant rise of serum cholesterol of about 11 mg/100 ml (0.29 mmole/liter). The dietary cholesterol did not influence serum triglyceride levels. The influence on serum cholesterol was much less than expected, based on several predictive formulas. It is concluded that the presence of a high content of linoleic acid in the diet reduces the effect of dietary cholesterol on serum cholesterol if the cholesterol is provided as egg yolk.     

Low-fat and high-monounsaturated fatty acid diets decrease plasma cholesterol ester transfer protein concentrations in young, healthy, normolipemic men

BACKGROUND: Cholesterol ester transfer protein (CETP) mediates the transfer of cholesteryl esters from HDL to apolipoprotein (apo) B-containing lipoproteins. The possible atherogenic role of this protein is controversial. Diet may influence plasma CETP concentrations. OBJECTIVE: The objective was to determine whether the changes in plasma lipids observed after consumption of 2 lipid-lowering diets are associated with changes in plasma CETP concentrations. DESIGN:: We studied 41 healthy, normolipidemic men over 3 consecutive 4-wk dietary periods: a saturated fatty acid-rich diet (SFA diet: 38% fat, 20% saturated fat), a National Cholesterol Education Program Step I diet (NCEP Step I diet: 28% fat, 10% saturated fat), and a monounsaturated fatty acid-rich diet (MUFA diet: 38% fat, 22% monounsaturated fat). Cholesterol content (27.5 mg/MJ) was kept constant during the 3 periods. Plasma concentrations of total, LDL, and HDL cholesterol; triacylglycerol; apo A-I and B; and CETP were measured at the end of each dietary period. RESULTS: Compared with the SFA diet, both lipid-lowering diets significantly decreased plasma total and LDL cholesterol, apo B, and CETP. Only the NCEP Step I diet lowered plasma HDL cholesterol. Positive, significant correlations were found between plasma CETP and total (r = 0.3868, P < 0.0001) and LDL (r = 0.4454, P < 0.0001) cholesterol and also between changes in CETP concentrations and those of total (r = 0.4543, P < 0.0001) and LDL (r = 0.4554, P < 0.0001) cholesterol. CONCLUSIONS: The isoenergetic substitution of a high-saturated fatty acid diet with an NCEP Step I or a high-monounsaturated fatty acid diet decreases plasma CETP concentrations.     

Dietary conjugated linoleic acid reduces lipid peroxidation by increasing oxidative stability in rats

The antioxidative effect of conjugated linoleic acid (CLA) was examined by determining lipid peroxidation and antioxidative enzyme activities. Male Sprague-Dawley rats were fed one of the experimental diets-normal diet, vitamin E-deficient control diet, 0.5% CLA vitamin E-deficient diet, or 1.5% CLA vitamin E-deficient diet for 5 wk. Hepatic thiobarbituric acid reactive substances (TBARS) were increased in the vitamin E-deficient control group, but they were was significantly lowered in the CLA groups. Similarly, hepatic glutathione peroxidase activity was increased in the vitamin E-deficient diet and reduced by CLA supplementation. In addition, CLA caused a significant decrease in superoxide dismutase activity while having no effect on catalase activity. Analyses of the fatty acid composition revealed that dietary CLA was incorporated into hepatic microsomal membrane dose-dependently. Compared to the vitamin E-deficient control, CLA resulted in significantly higher saturated and monounsaturated fatty acids (palmitic and oleic acids) while lowering levels of oxidation-susceptible polyunsaturated fatty acids (linoleic, linolenic, and arachidonic acids) in both plasma and hepatic membrane. The concentrations of plasma cholesterol and triacylglycerol (TG) were lower in the 1.5% CLA group than in other groups. These results suggest that dietary CLA has antiatherosclerotic and antioxidant activity by increasing oxidative stability in plasma and hepatic membrane in the vitamin E-deficient rats.     

Inulin attenuates atherosclerosis in apolipoprotein E-deficient mice

Effects of different inulin-type fructan fractions were studied on atherosclerotic plaque formation in male apo E-deficient mice. Thirty-two mice were randomly divided into four groups and received either a semi-purified sucrose-based diet (control group), or diets in which sucrose was replaced in part by various inulin-type fructans (10 g/100 g): long-chain inulin, oligofructose, or an oligofructose-enriched inulin for 16 weeks. The presence of atherosclerotic plaques was assessed by histomorphometry in the aortic sinus. The apo E-deficient mice fed long-chain inulin or an oligofructose-enriched inulin had about 35 % and 25 % less atherosclerotic lesion area compared with the control group, respectively. Feeding long-chain inulin significantly reduced plasma cholesterol concentrations (P<0.001), and the three inulin-type fructans reduced triacylglycerol (TAG) concentrations compared with the control group (P<0.001). Both the long-chain inulin and an oligofructose-enriched inulin significantly lowered hepatic cholesterol concentrations compared with the control diet (P<0.05). Hepatic TAG concentrations were significantly lower in all three groups fed the fructan-supplemented diets v. the control group (P<0.0001). The results of the present study suggest that inhibition of atherosclerotic plaque formation is more potent in the presence of long-chain inulin, either alone or in combination with oligofructose (an oligofructose-enriched inulin), and that this probably is related to changes in lipid metabolism.     

Manganese, iron and lipid interactions in rats

The interactive effects of manganese, iron and lipid on mineral status, manganese-dependent superoxide dismutase (MnSOD) activity and lipoprotein composition were investigated by feeding weanling rats two levels of manganese (0.4 or 56 micrograms Mn/g diet), two levels of iron (29 or 109 micrograms Fe/g diet) and either 12% high-linoleic acid safflower oil or 12% high-oleic acid safflower oil for 8 wk. Rats fed the manganese-deficient diets had decreased heart MnSOD activity; depressed tibia and kidney manganese concentrations; lowered plasma and high density lipoprotein (HDL) cholesterol, HDL protein and HDL apo E concentrations; and elevated HDL protein/cholesterol ratios. Ingestion of supplemental iron slightly decreased heart MnSOD activity and tibia and kidney manganese concentrations but had no effect on hematocrits or on plasma and HDL cholesterol levels. Rats fed the linoleic acid-rich rather than the oleic acid-rich oil had increased heart MnSOD activity but had unchanged plasma and HDL cholesterol levels. The decrease in plasma and HDL cholesterol levels with manganese deficiency appeared not to be a result of increased lipid peroxidation but may have resulted from decreased cholesterol synthesis and/or secretion.     

Phytosterol oxidation products are absorbed in the intestinal lymphatics in rats but do not accelerate atherosclerosis in apolipoprotein E-deficient mice

Phytosterol oxidation products (oxyphytosterols) are formed during the processing and storage of foods. However, it is unknown whether oxyphytosterols affect human health. To address these issues, we prepared beta-sitosterol and campesterol oxides, evaluated their lymphatic absorption in rats, and examined the effect of an oxyphytosterol diet on atherosclerosis in apolipoprotein (apo) E-deficient mice. The lymphatic absorption of cholesterol and 6 oxyphytosterols (7alpha-hydroxy, 7beta-hydroxy, beta-epoxy, alpha-epoxy, dihydroxy, and 7-keto) of beta-sitosterol or campesterol was assessed in thoracic duct-cannulated rats fed an AIN-93G-based diet containing 2.5 g of cholesterol, oxyphytosterols, or intact phytosterols per kg. Lymphatic recoveries (on a mass basis) of oxycampesterols (15.9 +/- 2.8%, n = 10) and oxysitosterols (9.12 +/- 1.77%, n = 10) were higher than for campesterol (5.47 +/- 1.02%, n = 12, P < 0.05) and beta-sitosterol (2.16 +/- 0.37%, n = 12, P < 0.05), but lower than for cholesterol (37.3 +/- 8.3%, n = 6, P < 0.05). Apo E-deficient mice were fed an AIN-93G-based diet containing 0.2 g oxyphytosterols or intact phytosterols per kg for 9 wk. Diet-derived oxyphytosterols accumulated in the serum, liver, and aorta. Furthermore, the oxyphytosterol diet increased oxycholesterol in the serum compared to the phytosterol diet. However, there was no significant difference between the 2 groups in the serum and aortic cholesterol concentration, the lesion area in the aortic root, or 8-iso-prostaglandin F2alpha concentration in the urine. These results indicate that exogenous oxyphytosterols are well-absorbed and accumulate in the body, but do not promote the development of atherosclerosis in apo E-deficient mice.     

不同脂肪酸负荷膳食对小鼠胆固醇代谢的影响

目的　为研究脂肪酸对胆固醇代谢可能的分子机制。方法　C5 7小鼠 75只 ,随机分为 5组 ,各组饲以相应配方饲料 6周。结果　与胆固醇膳食 (Chol)相比 ,胆固醇 多不饱和脂肪酸膳食 (Chol PUFA)可增加血清总胆固醇、机体总胆汁酸 (P <0 0 5 ) ,降低肝脏胆固醇 (P <0 0 5 ) ;胆固醇 单不饱和脂肪酸膳食 (Chol MUFA)动物血清总胆固醇不变 ,机体总胆汁酸明显增加 (P <0 0 5 ) ,肝脏胆固醇降低 (P <0 0 5 ) ;胆固醇 饱和脂肪酸 (Chol SFA)膳食可明显增加 (P <0 0 5 )血清总胆固醇和肝脏胆固醇 ,降低 (P <0 0 5 )机体总胆汁酸。此外 ,PUFA、MUFA和SFA均明显降低肝脏胆固醇 7α -羟化酶 (CYP7a1)mRNA和蛋白的表达。结论　膳食脂肪酸可通过CYP7a1调节机体胆固醇内稳态 ,多不饱和脂肪酸和单不饱和脂肪酸可诱导胆固醇转化为胆汁酸进而维持机体胆固醇在较低水平 ,而此过程中产生的大量胆汁酸又可反馈抑制CYP7a1的表达 ;相反 ,饱和脂肪酸可能通过直接抑制或不改变CYP7a1的表达 ,导致膳食胆固醇在体积的堆积     

The effect of a high cholesterol and saturated fat diet on serum high-density lipoprotein-cholesterol, apoprotein A-I, and apoprotein E levels in normolipidemic humans

The effects of a high cholesterol, high saturated fat diet on serum high density lipoprotein cholesterol, apo A-I, and apo E levels were studied in six normolipidemic subjects. The study was done on an outpatient basis and mixed natural foods normally consumed by humans were used. When compared with a low cholesterol (98 mg/day) high polyunsaturated fat (P/S ratio 1.6) diet, the high cholesterol (1021 mg/day), high saturated fat (P/S ratio 0.4) diet increased serum cholesterol (23%) by raising the cholesterol concentration in very low-density lipoproteins (59%), low-density lipoproteins (15%), and high-density lipoproteins (30%). The low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol ratio fell significantly from 1.78 to 1.58. The increased high-density lipoprotein-cholesterol was associated with an elevation of serum apo A-I but not apo E. Serum triglycerides did not change significantly.     

Interrelationship of plasma triglycerides and HDL size and composition in rats fed different dietary saturated fats

We investigated the relative effects of different dietary saturated fats on the size distribution, apolipoprotein (apo) and chemical composition of HDL in fasted rats. Male Sprague-Dawley rats (174 +/- 2 g) were fed diets containing 0.035% cholesterol and 16% fat (wt/wt) from corn oil (CO diet) or from 2% CO plus 14% butterfat (BF diet), beef tallow (BT diet), palm oil (PO diet) or coconut oil (CN diet) for 6 wk. Apparent lipid digestibility was significantly lower with the PO and BT diets vs. the CO, BF and CN diets. Plasma total cholesterol levels were significantly higher in rats fed the PO and BT diets than in rats fed the BF and CN diets but were not different among the PO-, BT- and CO-fed groups. Nondenaturing gradient gel electrophoresis immunoblot analysis indicated that HDL apo A-I and E resided on particles with significantly smaller modal diameters in rats fed all saturated fats compared with those fed the CO diet. Chemical analyses indicated that HDL generally contained proportionately less protein and more triglyceride, free cholesterol and apo E with saturated fat feeding than with CO diet feeding. Significantly higher plasma and VLDL triglyceride levels were noted with ingestion of the BT, PO or CN diet than with the CO diet. Butterfat feeding resulted in lower plasma triglycerides and HDL-esterified cholesterol than did feeding the other saturated fats. Very low density lipoprotein triglyceride concentrations were inversely correlated with HDL modal diameter of apo E containing lipoproteins (P less than 0.005). These data provide further evidence of the interrelationship of triglyceride and HDL metabolism and suggest that mechanisms independent of cholesterol ester transfer protein may mediate this response in rats.     

Eicosanoid production, thrombogenic ratio, and serum and LDL peroxides in normo- and hypercholesterolaemic post-menopausal women consuming two oleic acid-rich diets with different content of minor components

The present paper compares the effects of two monounsaturated oils, extra virgin olive oil (EVOO) and high-oleic acid sunflower oil (HOSO), on serum and LDL peroxides, eicosanoid production and the thrombogenic ratio (thromboxane (TX) B2:6-keto-prostaglandin F1alpha) in fourteen non-obese post-menopausal women. The subjects, mean age 63 (SD 11) years, were assigned to two consecutive oleic acid-rich 28 d dietary periods. EVOO and HOSO represented 62 % of the total lipid intake and were used as the only culinary fat during the first and second dietary periods respectively. Serum peroxides, plasma alpha-tocopherol and TXB2 levels in stimulated platelet-rich plasma (PRP-TXB2) were significantly higher (P < 0.01, P < 0.001, and P < 0.05, respectively) after the HOSO diet than after the EVOO diet. The relationship between the serum cholesterol level (< 6.21 mmol/l or > or = 6.21 mmol/l) and the type of dietary oil on eicosanoids, peroxides and alpha-tocopherol were evaluated by two-way ANOVA. Dietary oil significantly affected (P < 0.05) the PRP-TXB2 level, whereas serum and LDL peroxides were significantly affected (P < 0.001 and P < 0.01, respectively) by the serum cholesterol level. The plasma alpha-tocopherol level was significantly affected by the serum cholesterol level and the type of dietary oil (both P < 0.001). No significant relationships were found between serum cholesterol levels, serum peroxide or LDL peroxide levels, plasma alpha-tocopherol concentrations or alpha-tocopherol intakes with eicosanoid production or the thrombogenic ratio due to dietary changes. However, in spite of their higher alpha-tocopherol levels, hypercholesterolaemic subjects showed increased peroxidation in serum and LDL in comparison with normocholesterolaemic subjects on the HOSO diet in comparison with the EVOO diet. These findings suggest that differences in the type of minor compounds, as well as in the concentration of linoleic acid, in both these monounsaturated oils may play an important role in modulating eicosanoid production and lipoprotein peroxidation when they constitute a large proportion of the diet of post-menopausal women.     

Fish consumption shifts lipoprotein subfractions to a less atherogenic pattern in humans

The effect of fish consumption on plasma lipoprotein subfraction concentrations was studied in 22 men and women (age > 40 y). Subjects were provided an average American diet (AAD, 35% of energy as fat, 14% as saturated fat, and 35 mg cholesterol/MJ) for 6 wk before being assigned to a National Cholesterol Education Program (NCEP) Step 2 high-fish diet (n = 11, 26% of energy as fat, 4.5% as saturated fat, and 15 mg cholesterol/MJ) or a NCEP Step 2 low-fish diet (n = 11, 26% of energy as fat, 4.0% as saturated fat, and 11 mg cholesterol/MJ) for 24 wk. All food and drink were provided to study participants. Consumption of the high-fish NCEP Step 2 diet was associated with a significant reduction in medium and small VLDL, compared with the AAD diet, whereas the low-fish diet did not affect VLDL subfractions. Both diets significantly reduced LDL cholesterol concentrations, without modifying LDL subfractions. Both diets also lowered HDL cholesterol concentrations. However, the high-fish diet significantly lowered only the HDL fraction containing both apolipoprotein (apo) AI and AII (LpAI:AII) and did not change HDL subfractions assessed by NMR, whereas the low-fish diet significantly lowered the HDL fraction containing only apo AI (LpAI) and the large NMR HDL fractions, resulting in a significant reduction in HDL particle size. Neither diet affected VLDL and LDL particle size. Our data indicate that within the context of a diet restricted in fat and cholesterol, a higher fish content favorably affects VLDL and HDL subspecies.     

Roles of omega 3 fatty acids and chronic ethanol in the regulation of plasma and liver lipids and plasma apoproteins A1 and E in rats

Relative effects of feeding ethanol and/or omega 3 fatty acid-rich fish oil for 6 wk on body lipids and lipoproteins were investigated. Ethanol increased plasma cholesterol (P less than 0.06) and triglycerides (P less than 0.0005), whereas fish oil decreased plasma cholesterol (P less than 0.005) and triglycerides (P less than 0.02). Liver cholesterol and triglycerides were increased by ethanol (P less than 0.0001) while fish oil decreased liver cholesterol (P less than 0.01) but not triglycerides. Based on Scheffé contrasts (P less than 0.05), fish oil blocked the increases in liver cholesterol and triglycerides caused by ethanol. Substitution of normal dietary fat with omega 3 fatty acid-rich fat in ethanol-fed animals lowered plasma cholesterol by 29% (P less than 0.001) and triglycerides by 30% (P less than 0.05) within 2 wk. Plasma apo A1 was increased by ethanol (P less than 0.001) and decreased by fish oil (P less than 0.002). Plasma total apo E was unaffected by either ethanol or fish oil. However, HDL apo E was decreased by ethanol (P less than 0.04) and increased by fish oil (P less than 0.02). Scheffé contrasts (P less than 0.05) also showed that plasma apo A was increased by ethanol regardless of whether the animals were consuming regular fat (1.72-fold) or fish oil fat (1.49-fold). Thus, omega 3 fatty acids can not only prevent but also reverse many of the lipid and lipoprotein abnormalities caused by alcohol abuse in the rat.     

Supplementation of diets with the black rice pigment fraction attenuates atherosclerotic plaque formation in apolipoprotein e deficient mice

Apolipoprotein (apo)E-deficient mice were used to study the antiatherogenic effect of black rice pigment fraction (BRF) and the possible mechanisms by which it inhibits atherogenesis. The apoE-deficient mice (n = 45) were randomly divided into three groups and received AIN-93G diet (positive group), AIN-93G with 5 g of black rice pigment fraction/100 g (BRF group) and AIN-93G with 5 g of white rice outer layer fraction/100 g (WRF group) for 16 wk. C57BL/6J mice (n = 15) received AIN-93G and were used as a control group. Blood samples were collected for measurement of lipid concentration, antioxidized LDL antibody and nitric oxide concentration. Livers were extracted for determination of cholesterol concentrations, and aortas were used to determine cholesterol concentrations and inducible nitric oxide synthase protein and mRNA expression. Hearts were used to assess atherosclerotic plaque formation. The apoE-deficient mice fed the black rice pigment fraction diet had 48% (P < 0.01) less atherosclerotic lesion area compared with apoE-deficient mice fed only the AIN-93G diet and 46% (P < 0.01) less lesion area compared with mice fed the white rice outer layer fraction diet. This observation corresponded with significantly (P < 0.05) lower total serum cholesterol, lower liver and aorta cholesterol (P < 0.01) and higher HDL cholesterol (P < 0.05) concentrations and lower (P < 0.05) antioxidized LDL antibody titer in apoE-deficient mice fed the black rice pigment fraction diet compared with positive and WRF groups. Notwithstanding this, mice fed the black rice pigment fraction diet also had lower CD4(+) T lymphocyte expression (P < 0.05) and weaker inducible nitric oxide synthase expression (P < 0.05) compared with mice fed the AIN-93G diet and the white rice outer layer fraction diet, respectively. We concluded that the inhibition of atherosclerotic lesions of the black rice pigment fraction is attributed to the improvement in cholesterol accumulation and reduction in oxidative stress and inflammation.     

Effects of cranberry powder on biomarkers of oxidative stress and glucose control in db/db mice

Increased oxidative stress in obese diabetes may have causal effects on diabetic complications, including dyslipidemia. Lipopolysccharides (LPS) along with an atherogenic diet have been found to increase oxidative stress and insulin resistance. Cranberry has been recognized as having beneficial effects on diseases related to oxidative stress. Therefore, we employed obese diabetic animals treated with an atherogenic diet and LPS, with the aim of examining the effects of cranberry powder (CP) on diabetic related metabolic conditions, including lipid profiles, serum insulin and glucose, and biomarkers of oxidative stress. Forty C57BL/KsJ-db/db mice were divided into the following five groups: normal diet + saline, atherogenic diet + saline, atherogenic diet + LPS, atherogenic diet + 5% CP + LPS, and atherogenic diet + 10% CP + LPS. Consumption of an atherogenic diet resulted in elevation of serum total cholesterol and atherogenic index (AI) and reduction of high density lipoprotein (HDL)-cholesterol. However, with 10% CP, the increase in mean HDL-cholesterol level was close to that of the group with a normal diet, whereas AI was maintained at a higher level than that of the group with a normal diet. LPS induced elevated serum insulin level was lowered by greater than 60% with CP (P < 0.05), and mean serum glucose level was reduced by approximately 19% with 5% CP (P > 0.05). Mean activity of liver cytosolic glutathione peroxidase was significantly increased by LPS injection, however it was reduced back to the value without LPS when the diet was fortified with 10% CP (P < 0.05). In groups with CP, a reduction in mean levels of serum protein carbonyl tended to occur in a dose dependent manner. Particularly with 10% CP, a reduction of approximately 89% was observed (P > 0.05). Overall results suggest that fortification of the atherogenic diet with CP may have potential health benefits for obese diabetes with high oxidative stress, by modulation of physical conditions, including some biomarkers of oxidative stress.     

Oxidized fatty acids promote atherosclerosis only in the presence of dietary cholesterol in low-density lipoprotein receptor knockout mice

Studies suggest that heated oils contribute to the presence of oxidized components in the circulating lipoproteins and to the development of atherosclerosis in animals. We evaluated the effects of 11-13 wk of consumption of a well defined dietary oxidized fatty acid, 13-hydroxylinoleic acid (13-HODE) (8 mg), on atherosclerotic lesion development and plasma cholesterol concentrations in mice fed diets varying in fat and cholesterol contents. LDL receptor knockout mice were used in two feeding studies. In study 1, oxidized fatty acid consumption in association with a high fat diet increased aortic lesion areas by >100% (P < 0.05). Surprisingly, oxidized fatty acid intake also tended to increase plasma total cholesterol (P = 0.12) and LDL cholesterol (P < 0.05) as well as oxidative stress as measured by higher levels of autoantibodies to oxidatively modified proteins (P = 0.008). However, in mice fed a nonpurified diet, oxidized fatty acids were not atherogenic and may even have been beneficial, as indicated by a lower plasma triglyceride (TG) concentration (P < 0.05). In study 2, mice were fed either a high fat, medium fat or low fat diet to evaluate whether the increase in aortic lesions due to oxidized fatty acid consumption in study 1 was a result of the associated higher plasma total and LDL cholesterol concentrations. In study 2, 13-HODE-treated mice in the medium and low fat diet groups but not those fed the high fat diet had larger atherosclerotic lesions (P < 0.05). Additionally, plasma total and LDL cholesterol as well as TG were not affected by HODE treatment. However, the total cholesterol:HDL cholesterol ratio was higher in treated mice (P < 0.05) and HDL cholesterol was lower in HODE-treated mice that were fed the low fat diet (P < 0.05). Our results suggest that, in mice fed cholesterol, oxidized fatty acids may be atherogenic, both in terms of increased oxidative stress (as seen in study 1) and by increasing the atherogenicity of the plasma cholesterol profile.     

Fatty acid saturation of the diet and plasma lipid concentrations, lipoprotein particle concentrations, and cholesterol efflux capacity

BACKGROUND: The fatty acid content and saturation degree of the diet can modulate HDL composition and cholesterol efflux. OBJECTIVE: We studied the modifications in plasma lipoprotein particles and serum capacity to stimulate cholesterol efflux induced by different fatty acids. DESIGN: Seventeen women and 24 men followed in the same sequence 4 diets containing 35% of total energy as fat. The saturated fat diet contained 17% palm oil; the monounsaturated fat diet, 20.9% olive oil; the n-6 polyunsaturated fat diet, 12.5% sunflower oil; and the n-3 polyunsaturated fat diet, sunflower oil supplemented with 4-4.5 g fish oil/d. Each phase lasted 4-5 wk. RESULTS: In both sexes, apolipoprotein (apo) A-I concentrations were significantly lower with unsaturated fat diets than with the saturated fat diet, but concentrations of lipoproteins containing only apo A-I (Lp A-I) were lower only in the men. Concentrations of lipoproteins containing both apo A-I and apo A-II (Lp A-I:A-II) were lower with both polyunsaturated fat diets in the women but significantly higher in the men. Lp E concentrations were significantly higher with the 2 polyunsaturated fat diets. Lp E non-B particle concentrations were not modified in the men but were significantly higher in the women in both polyunsaturated fat phases. Lp C-III concentrations were higher with the saturated fat diet only in the men. The serum samples taken after the n-3 polyunsaturated fat phase were the most efficient for extracting cellular cholesterol in both sexes. CONCLUSIONS: The monounsaturated and polyunsaturated fat diets were healthier, producing a better lipid profile. The n-3 polyunsaturated fat diet increased the capacity of serum to promote the efflux of cholesterol from cells in culture.     

Linoleic acid lowers LDL cholesterol without a proportionate displacement of saturated fatty acid

We tested the specificity of the plasma cholesterol-lowering effect of linoleic acid in a comparison of linoleate-rich and saturated fatty acid-rich foods. Twelve mildly hypercholesterolemic men and women ate the two diets for three weeks each in a random cross-over design, after a two-week baseline period. A linoleic acid-rich supplement was added to the baseline diet so that the saturated and monounsaturated fatty acid content did not change significantly. Despite the consequent increase in total fat intake, the linoleate-rich diet (23 per cent energy from polyunsaturated fatty acids) significantly lowered plasma total and low-density lipoprotein (LDL) cholesterol (-8 per cent and -14 per cent respectively), while high-density lipoprotein (HDL) cholesterol rose 8 per cent. The direction of these changes was similar in all 12 subjects. Compared with a supplement that raised dietary saturated fatty acids to 30 per cent energy, the linoleate acid-rich diet gave lower total cholesterol (-14 per cent), LDL cholesterol (-18 per cent) and HDL cholesterol (-12 per cent) concentrations. Linoleic acid lowers LDL cholesterol even when saturated fatty acids are not significantly displaced and substantially more when there is such displacement.     

Effect of leptin infusion on insulin sensitivity and lipid metabolism in diet-induced lipodystrophy model mice

Background

Amyloid-β (Aβ), a key protein found in amyloid plaques of subjects with Alzheimer's disease is expressed in the absorptive epithelial cells of the small intestine. Ingestion of saturated fat significantly enhances enterocytic Aβ abundance whereas fasting abolishes expression. Apolipoprotein (apo) E has been shown to directly modulate Aβ biogenesis in liver and neuronal cells but it's effect in enterocytes is not known. In addition, apo E modulates villi length, which may indirectly modulate Aβ as a consequence of differences in lipid absorption. This study compared Aβ abundance and villi length in wild-type (WT) and apo E knockout (KO) mice maintained on either a low-fat or high-fat diet. Wild-type C57BL/6J and apo E KO mice were randomised for six-months to a diet containing either 4% (w/w) unsaturated fats, or chow comprising 16% saturated fats and 1% cholesterol. Quantitative immunohistochemistry was used to assess Aβ abundance in small intestinal enterocytes. Apo E KO mice given the low-fat diet had similar enterocytic Aβ abundance compared to WT controls.

Results

The saturated fat diet substantially increased enterocytic Aβ in WT and in apo E KO mice, however the effect was greater in the latter. Villi height was significantly greater in apo E KO mice than for WT controls when given the low-fat diet. However, WT mice had comparable villi length to apo E KO when fed the saturated fat and cholesterol enriched diet. There was no effect of the high-fat diet on villi length in apo E KO mice.

Conclusion

The findings of this study are consistent with the notion that lipid substrate availability modulates enterocytic Aβ. Apo E may influence enterocytic lipid availability by modulating absorptive capacity.     

Essential fatty acid-rich diets protect against striatal oxidative damage induced by quinolinic acid in rats

Essential fatty acids have an important effect on oxidative stress-related diseases. The Huntington's disease (HD) is a hereditary neurologic disorder in which oxidative stress caused by free radicals is an important damage mechanism. The HD experimental model induced by quinolinic acid (QUIN) has been widely used to evaluate therapeutic effects of antioxidant compounds. The aim of this study was to test whether the fatty acid content in olive- or fish-oil-rich diet prevents against QUIN-related oxidative damage in rats. Rats were fed during 20 days with an olive- or a fish-oil-rich diet (15% w/w). Posterior to diet period, rats were striatally microinjected with QUIN (240?nmol/µl) or saline solution. Then, we evaluated the neurological damage, oxidative status, and gamma isoform of the peroxisome proliferator-activated receptor (PPARγ) expression. Results showed that fatty acid-rich diet, mainly by fish oil, reduced circling behavior, prevented the fall in GABA levels, increased PPARγ expression, and prevented oxidative damage in striatal tissue. In addition none of the enriched diets exerted changes neither on triglycerides or cholesterol blood levels, nor or hepatic function. This study suggests that olive- and fish-oil-rich diets exert neuroprotective effects.     

Metabolism of cholesterol is altered in the liver of C3H mice fed fats enriched with different C-18 fatty acids.

We examined whether the degree of saturation of C-18 fatty acids influenced hepatic cholesterol metabolism in C3H mice. The mice were fed diets containing 20 g/100 g fat, enriched in stearic (18:0), oleic (18:1) or linoleic acid (18:2) with or without 1 g/100 g cholesterol. Plasma total cholesterol concentration was lower in mice fed the 18:0 diet relative to those fed the 18:1- or 18:2-enriched diets (P < 0.05) regardless of dietary cholesterol supplementation. Dietary cholesterol significantly raised hepatic total cholesterol concentration (P < 0.05) in those fed the 18:1- and 18:2-enriched diets, but not in mice fed the 18:0-enriched diet. Dietary cholesterol raised biliary cholesterol concentration (P < 0. 05) in mice fed the 18:1- and 18:2-enriched diets, but not in mice fed the 18:0-enriched diet. The cholesterol saturation index was variably affected by the fat diets. Feeding diets containing cholesterol suppressed the hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) activity and induced acyl coenzyme A:cholesterol acyl transferase (ACAT) activity compared with feeding diets without cholesterol (P < 0.05), indicating that the liver was exposed to dietary cholesterol. Hepatic ACAT activity was lower in mice fed the 18:0-enriched diet compared with those fed the 18:1- or 18:2-enriched diets (P < 0.05). Addition of cholesterol to the 18:1 diet induced the largest increase of hepatic ACAT activity, and this was associated with the enrichment of VLDL with cholesterol. Varying the degree of saturation of C-18 fatty acids influences the metabolism and disposition of hepatic cholesterol.