Genetic variation at the apoA-IV gene locus and response to diet in familial hypercholesterolemia

Plasma lipid response to dietary fat and cholesterol is, in part, genetically controlled. The apolipoprotein A-IV (apoA-IV protein; APOA4, gene) has been shown to influence the response to dietary changes in normolipidemic individuals. The response to diet in subjects with familial hypercholesterolemia (FH) is also variable, and no studies are available on the influence of APOA4 mutations on dietary response in these subjects. We studied the effect of 2 common apoA-IV genetic variants (Gln360-->His and Thr347-->Ser) on the lipid response to the National Cholesterol Education Program type I (NCEP-I) diet in 67 FH heterozygotes (43 women and 24 men). Subjects were studied at baseline (after consuming for 1 month a diet with 35% fat [10% saturated] and 300 mg/d cholesterol) and after 3 months of consuming a low-fat diet. No sex-related differences were found, and results were combined for men and women. The APOA4-360 mutation was assessed in 67 subjects, 51 with genotype 1/1 and 16 with genotype 1/2. The APOA4-2 allele was associated with marginally significantly lower (P=0.049) low density lipoprotein (LDL) cholesterol levels and significantly lower (P=0.027) apoB levels independent of diet effects. After consuming an NCEP-I diet, carriers of the APOA4-2 allele showed a significantly lower reduction in apoB concentration (6.2%) than 1/1 subjects (14.1%; P=0.036); however, no significant differences in response were noted for LDL cholesterol. The APOA4-347 mutation was assessed in 63 individuals, 44 with the A/A allele and 19 with the A/T and T/T alleles. No significant differences were observed in baseline or post-NCEP-I diet values for these 2 groups in total, LDL, and high density lipoprotein cholesterol and plasma apoB levels. After dietary intervention, A/A individuals showed significant reductions in plasma triglyceride and very low density lipoprotein cholesterol levels; no changes were found in carriers of the T allele. Haplotype analysis suggested that in these FH subjects, the APOA4-360-2 allele was associated with lower plasma lipid levels during the NCEP-I diet period, whereas no significant effects were observed for the APOA4-347-T allele.     

The role of reproductive factors and use of oral contraceptives in the aetiology of breast cancer in women aged 50 to 74 years

BACKGROUND: We examined the cholesterol-lowering effects of a proprietary Chinese red-yeast-rice supplement in an American population consuming a diet similar to the American Heart Association Step I diet using a double-blind, placebo-controlled, prospectively randomized 12-wk controlled trial at a university research center. OBJECTIVE: We evaluated the lipid-lowering effects of this red-yeast-rice dietary supplement in US adults separate from effects of diet alone. DESIGN: Eighty-three healthy subjects (46 men and 37 women aged 34-78 y) with hyperlipidemia [total cholesterol, 5.28-8.74 mmol/L (204-338 mg/dL); LDL cholesterol, 3.31-7.16 mmol/L (128-277 mg/dL); triacylglycerol, 0.62-2.78 mmol/L (55-246 mg/dL); and HDL cholesterol 0.78-2.46 mmol/L (30-95 mg/dL)] who were not being treated with lipid-lowering drugs participated. Subjects were treated with red yeast rice (2.4 g/d) or placebo and instructed to consume a diet providing 30% of energy from fat, <10% from saturated fat, and <300 mg cholesterol daily. Main outcome measures were total cholesterol, total triacylglycerol, and HDL and LDL cholesterol measured at weeks 8, 9, 11, and 12. RESULTS: Total cholesterol concentrations decreased significantly between baseline and 8 wk in the red-yeast-rice-treated group compared with the placebo-treated group [(x+/-SD) 6.57+/-0.93 mmol/L (254+/-36 mg/dL) to 5.38+/-0.80 mmol/L (208+/-31 mg/dL); P < 0.001]. LDL cholesterol and total triacylglycerol were also reduced with the supplement. HDL cholesterol did not change significantly. CONCLUSIONS: Red yeast rice significantly reduces total cholesterol, LDL cholesterol, and total triacylglycerol concentrations compared with placebo and provides a new, novel, food-based approach to lowering cholesterol in the general population.     

Effect of long-term olive oil dietary intervention on postprandial triacylglycerol and factor VII metabolism

Although the beneficial effects of Mediterranean-type diets, which are rich in olive oil, a good source of monounsaturated fatty acids (MUFAs), are generally accepted, little is known about the effects of long-term dietary MUFA intake on postprandial lipoprotein metabolism and hemostasis. This study used a single-blind, randomized, crossover design to investigate the relative effects of a long-term dietary olive oil intervention and a control [saturated fatty acid (SFA)-enriched] diet on postprandial triacylglycerol metabolism and factor VII activity. The postprandial response to a standard test meal was investigated in 23 healthy men who adhered to both diets for 8 wk. cis-MUFAs were successfully substituted for SFAs in the MUFA diet without affecting total dietary fat or energy intakes. The long-term dietary MUFA intervention significantly reduced plasma and LDL-cholesterol concentrations (P = 0.01). Postprandial triacylglycerol concentrations were significantly greater in the early postprandial period after the MUFA diet (P = 0.003). Postprandial factor VII activation and the concentration of the factor VII antigen were significantly lower after the MUFA diet (P = 0.04 and P = 0.006, respectively). This study showed that isoenergetic substitution of MUFAs for SFAs reduces plasma cholesterol and reduces the degree of postprandial factor VII activation. The alterations in the postprandial triacylglycerol response suggest a greater rate of dietary fat absorption and postprandial triacylglycerol metabolism after a diet rich in MUFAs. This study presents new insights into the biochemical basis of the beneficial effects associated with long-term dietary MUFA consumption, which may explain the lower rates of coronary mortality in Mediterranean regions.     

An essential role for gamma interferon in innate resistance to Shigella flexneri infection

The purpose of this experiment was to study endurance performance and substrate storage and utilization in fat- or carbohydrate-fed rats. Ninety-nine rats were randomly divided into three groups and over 4 wk were fed either a carbohydrate-rich [CHO; 10% total energy content in the diet (E%) fat, 20 E% protein, 70 E% carbohydrate] diet or one of two fat-rich diets (65 E% fat, 20 E% protein, 15 E% carbohydrate) containing either saturated (Sat) or monounsaturated fatty acids (Mono). Each dietary group was randomly assigned to a trained (6 days/wk, progressive to 60 min, 28 m/min at a 10% incline) or a sedentary group. Rats were killed either before or after a treadmill endurance run to exhaustion. Training increased endurance (206%), but diet composition did not affect endurance in either trained or sedentary rats. beta-Hydroxyacyl-CoA dehydrogenase activity was increased in fat-fed but not carbohydrate-fed rats (P < 0.05). Respiratory exchange ratio during the initial phase of exercise was lower after the Mono compared with the Sat diet (P < 0. 05) and higher after the CHO than the Sat diet (P < 0.05). Thus adaptation to a high-fat diet containing a moderate amount of carbohydrates did not induce enhanced endurance in either trained or untrained rats; however, substrate utilization was modulated by both amount and type of dietary fat during the initial stage of exercise in trained and sedentary rats.     

Impact of gender on the metabolism of apolipoprotein A-I in HDL subclasses LpAI and LpAI:AII in older subjects

The behavior of apolipoprotein (apo) A-I in lipoprotein (Lp) AI and LpAI:AII was studied in 11 postmenopausal females and 11 males matched for plasma triglyceride and total cholesterol levels. Subjects consumed a baseline diet [35% fat (14% saturated, 15% monounsaturated, and 7% polyunsaturated), 15% protein, 49% carbohydrate, and 147 mg cholesterol/1000 kcal] for 6 weeks before the start of the kinetic study. At the end of the diet period, using a primed-constant infusion of [5,5,5-2H3]leucine, residence times (RT) and secretion rates (SR) of apoA-I were determined in 2 subpopulations of high-density lipoprotein (HDL) particles, LpAI and LpAI:AII. Plasma total cholesterol, low-density lipoprotein cholesterol, and triglyceride concentrations were similar in males and females. The mean plasma HDL cholesterol concentration in males (1.14 +/- 0.23 mmol/L; mean +/- SD) was lower than in females (1.42 +/- 0.18 mmol/L; P =. 0034). Similarly, the mean plasma concentration of apoA-I in males (130 +/- 21 mg/dL) was lower than that in females (150 +/- 19 mg/dL; P = .0421). The RT of apoA-I in either LpAI or LpAI:AII was similar between men and women. Despite the higher plasma apo A-I levels in female compared with male subjects, total apoA-I and apoA-I in LpAI and LpAI:AII pool sizes were similar between the two groups, attributable to the lower body weight of the female subjects. The mean SR of total apoA-I in males (8.5 +/- 2.7 mg.kg-1.d-1) was 22% lower than in females (10.9 +/- 2.3 mg.kg-1.d-1; P = .0389). The SR of both apoA-I in LpAI and LpAI:AII was lower in males than females, although the differences did not reach statistical significance. These data suggest that the difference observed in HDL cholesterol concentration between males and females is attributable to SR of apoA-I and not the catabolic rate.     

Effect of a stearic acid-rich, structured triacylglycerol on plasma lipid concentrations

BACKGROUND: Structured lipids are being incorporated into foods to reduce their energy value. One such lipid is rich in stearic acid. OBJECTIVE: The objective of this study was to compare the effects on plasma lipids of a stearic acid-rich triacylglycerol and a fat rich in palmitic acid in hypercholesterolemic subjects. DESIGN: Fifteen subjects with an average plasma cholesterol concentration of 6.13 +/- 0.80 mmol/L initially ate a low-fat diet for 2 wk (run-in period), followed in random order and blinded fashion by 2 high-fat diets (for 5 wk each) containing foods derived from margarines rich either in palmitic acid or in the structured, stearic acid-rich triacylglycerol. RESULTS: Plasma cholesterol concentrations with the low-fat, the stearic acid-rich, and the palmitic acid-rich diets were not significantly different (5.35 +/- 0.83, 5.41 +/- 0.78, and 5.52 +/- 0.68 mmol/L, respectively) but were significantly lower (P < 0.001) than those measured during the habitual diet period (ie, 2 wk before the study began). Neither HDL cholesterol nor plasma triacylglycerol differed significantly among the 3 study diets. CONCLUSION: A similar increase in the intake of stearic and palmitic acids (differing by approximately 5% of total energy) to ensure a high fat intake resulted in plasma total and LDL-cholesterol concentrations that did not differ significantly from concentrations measured during a period of low-fat intake.     

Effects of two low-fat diets, high and low in polyunsaturated fatty acids, on plasma lipid peroxides and serum vitamin E levels in free-living hypercholesterolaemic men

Diet enriched with polyunsaturated fat may increase the susceptibility of LDL to oxidation. Therefore the effects of two low-fat diets on plasma lipid peroxides in free-living mildly hypercholesterolaemic men (n = 37) were investigated in a randomized single-blind 28-week study. Composition of the diets were (1) American Heart Association (AHA) type 32/10:8:8 (indicating percentages of energy from total fat/saturated fat:monoenes:polyenes in actual diet); (2) low-fat 30/12:8:3. The subjects kept 3-day dietary records five times during the study to estimate the intake of nutrients. Plasma lipid peroxides were measured photometrically as the thiobarbituric-acid reactive substances (TBARS). Levels of serum vitamin E during the study were also determined. Mean change (+/- SD) in serum low density lipoprotein (LDL) cholesterol was similar in both groups (-0.32 +/- 0.76 vs -0.32 +/- 0.87 mmol/l) (AHA type vs low-fat). Level of TBARS decreased (P < 0.05) during the AHA type diet (-8.4 +/- 37.1%) (mean +/- SD) and increased (P = 0.228) during the low-fat diet (+8.7 +/- 27.0%) from 0 to 6 months. The mean intake of total active tocopherols was greater (14.7 +/- 3.7 mg) during the AHA type diet compared to the low-fat diet (7.8 +/- 2.1 mg). Serum vitamin E to LDL cholesterol ratio increased from 8.9 +/- 2.9 to 9.6 +/- 2.4 nmol/mmol (0 vs 6 months) (P = 0.07) during the AHA type diet and from 8.6 +/- 2.6 to 9.3 +/- 2.4 nmol/mmol (P = 0.159) during the low-fat diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of psyllium in hypercholesterolemia at two monounsaturated fatty acid intakes

We performed two studies to determine whether the lipid-lowering effect of viscous soluble fiber was modified by monounsaturated fatty acid (MUFA). First, psyllium (1.4 g/MJ) was compared with wheat bran (control) in 1-mo metabolic diets by using a randomized crossover design (n = 32 hyperlipidemic subjects). The background diet contained approximately 6% of energy as MUFA (20% of total fat). The second study (n = 27 hyperlipidemic subjects) was similar to the first but the background diet contained approximately 12% MUFA (29% of total fat) because of the addition of canola oil. At both fat intakes, psyllium resulted in significant reductions in total, low-density-lipoprotein (LDL), and high-density-lipoprotein (HDL) cholesterol compared with the wheat bran control. For the psyllium diet at 6% compared with 12% MUFA, the decreases in LDL cholesterol were 12.3 +/- 1.5% (P < 0.001) and 15.3 +/- 2.4% (P < 0.001), respectively. With the higher-MUFA diet triacylglycerol fell significantly over the control phase (16.6 +/- 5.5%, P = 0.006) and the ratio of LDL to HDL cholesterol fell significantly over the psyllium phase (7.3 +/- 2.8%, P = 0.015). Psyllium and MUFA intakes were negatively related to the percentage change in the ratio of LDL to HDL cholesterol (r = -0.34, P = 0.019 and r = -0.44, P = 0.002, respectively). Chenodeoxycholate synthesis rate increased (30 +/- 13%, P = 0.038) with the psyllium diet in the 12 subjects in whom this was assessed. We conclude that psyllium lowered LDL- and HDL-cholesterol concentrations similarly at both MUFA intakes. However, there may be some advantage in combining soluble fiber and MUFA to reduce the ratio of LDL to HDL cholesterol.     

Psyllium-enriched cereals lower blood total cholesterol and LDL cholesterol, but not HDL cholesterol, in hypercholesterolemic adults: results of a meta-analysis

We conducted a meta-analysis to determine the effect of consumption of psyllium-enriched cereal products on blood total cholesterol (TC), LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) levels and to estimate the magnitude of the effect among 404 adults with mild to moderate hypercholesterolemia (TC of 5.17-7.8 mmol/L) who consumed a low fat diet. Studies of psyllium cereals were identified by a computerized search of MEDLINE and Current Contents and by contacting United States-based food companies involved in psyllium research. Published and unpublished studies were reviewed by one author and considered eligible for inclusion in the meta-analysis if they were conducted in humans, were randomized, controlled experiments, and included a control group that ate cereal providing /=50 y) on blood lipids. The meta-analysis showed that subjects who consumed a psyllium cereal had lower TC and LDL-C concentrations [differences of 0.31 mmol/L (5%) and 0.35 mmol/L (9%), respectively] than subjects who ate a control cereal; HDL-C concentrations were unaffected in subjects eating psyllium cereal. There was no effect of sex, age or menopausal status on blood lipids. Results indicate that consuming a psyllium-enriched cereal as part of a low fat diet improves the blood lipid profile of hypercholesterolemic adults over that which can be achieved with a low fat diet alone.     

Long-term effect of soluble-fiber foods on postprandial fat metabolism in dyslipidemic subjects with apo E3 and apo E4 genotypes

To determine the long-term effect of soluble fiber on postprandial fat metabolism, we studied 33 dyslipidemic subjects, 16 with apolipoprotein (apo) E3/3 (E3) and 17 with E3/4 or E4/4 (E4) genotypes. They ate preweighed low-fat (20% of energy), high-fiber (> 5.7 g/MJ) diets for two 4-mo periods separated by a 2-mo washout period according to a randomized, crossover design. One diet contained foods rich in insoluble fiber and the other foods rich in soluble fiber. On 1 d during the last 2 wk of each diet, subjects ingested a standard, fiber-free, fatty liquid meal containing retinyl palmitate as a marker of intestinally derived lipoproteins. Plasma samples were obtained at hourly intervals for 10 h. Compared with the insoluble-fiber diet, soluble fiber reduced fasting plasma total cholesterol in both E3 (6.6 +/- 2.1%, P = 0.007)and E4 subjects (5.6 +/- 2.1%, P = 0.017). Soluble fiber increased fecal total bile acid output in both E3 (76 +/- 18%, P < 0.001) and E4 subjects (85 +/- 19%, P < 0.001). The incremental area under the chylomicron triacylglycerol response curve was significantly greater after soluble fiber than after insoluble fiber in E3 (3.56 +/- 0.56 compared with 2.87 +/- 0.38 mmol x h/L, respectively, P = 0.046) but not in E4 subjects (5.19 +/- 0.78 compared with 4.92 +/- 0.81 mmol x h/L). Kinetic analysis suggested an increase in retinyl palmitate absorption in E3 subjects after soluble fiber, but no difference in E4 subjects. These results suggest that a long-term increase in dietary soluble fiber has no effect on postprandial fat metabolism in subjects with an apo E3/4 or E4/4 genotype. However, soluble fiber enhances apparent fat absorption in E3 subjects, which could be due to an increased bile acid pool and increased micelle formation.     

Inverse association of dietary fat with development of ischemic stroke in men

CONTEXT: A few ecological and cohort studies in Asian populations suggest an inverse association of the intake of both fat and saturated fat with risk of stroke. However, data among western populations are scant. OBJECTIVE: To examine the association of stroke incidence with intake of fat and type of fat among middle-aged US men during 20 years of follow-up. DESIGN AND SETTING: The Framingham Heart Study, a population-based cohort study. PARTICIPANTS: A total of 832 men, aged 45 through 65 years, who were free of cardiovascular disease at baseline (1966-1969). MEASUREMENTS AND DATA ANALYSIS: The diet of each subject was assessed at baseline by a single 24-hour dietary recall, from which intakes of energy and macronutrients were estimated. In Kaplan-Meier analyses, we calculated age-adjusted cumulative incidence rates of stroke. Using Cox regression, we estimated stroke incidence relative risks during 20 years of follow-up. MAIN OUTCOME MEASURE: Incidence of ischemic stroke, which occurred in 61 subjects during the follow-up period. RESULTS: Mean intakes were 10975 kJ for energy; 114 g (39% of energy) for total fat; 44 g (15%) for saturated fat; 46 g (16%) for monounsaturated fat; and 16 g (5%) for polyunsaturated fat. Risk of ischemic stroke declined across the increasing quintile of total fat (log-rank trend P=.008), saturated fat (P=.002), and monounsaturated fat (P=.008) but not polyunsaturated fat (P=.33). The age- and energy-adjusted relative risk for each increment of 3% of energy from total fat was 0.85 (95% confidence interval [CI], 0.78-0.94); for an increment of 1% from saturated fat, 0.91 (95% CI, 0.85-0.98); and for 1% from monounsaturated fat, 0.89 (95% CI, 0.83-0.96). Adjustment for cigarette smoking, glucose intolerance, body mass index, blood pressure, blood cholesterol level, physical activity, and intake of vegetables and fruits and alcohol did not materially change the results. Too few cases of hemorrhagic stroke (n=14) occurred to draw inferences. CONCLUSION: Intakes of fat, saturated fat, and monounsaturated fat were associated with reduced risk of ischemic stroke in men.     

Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study

CONTEXT: Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons. OBJECTIVE: To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels. DESIGN: A randomized, double-blind, placebo-controlled trial. SETTING: Outpatient clinics in Texas. PARTICIPANTS: A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51 st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). INTERVENTION: Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat, low-cholesterol diet. MAIN OUTCOME MEASURES: First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. RESULTS: After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (1 83 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P =.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups. CONCLUSIONS: Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.     

A peptide isolated from a random phage peptide library is a structural mimic to the P1, P4-diadenosine 5''-tetraphosphate binding site on its receptor

The S2 allele of the SstI polymorphism of the apolipoprotein (apo) C-III gene has been associated with elevated triacylglycerol concentrations, high blood pressure, and increased risk of coronary artery disease, all of which are characteristic of an insulin-resistant state. To study the effect of this mutation on carbohydrate metabolism in healthy persons, we gave 41 male subjects 3 consecutive diets. The first was rich in saturated fat [15% protein, 47% carbohydrate, 38% fat (20% saturated)], the second was a National Cholesterol Education Program Step 1 diet [15% protein, 57% carbohydrate, 28% fat (< 10% saturated)], and the last was rich in monounsaturated fat [15% protein, 47% carbohydrate, 38% fat (22% monounsaturated, < 10% saturated)]. At the end of each dietary period, subjects received an oral-glucose-tolerance test (OGTT). Apo C-III genotype significantly affected basal glucose concentrations (P < 0.045) and insulin concentrations after the OGTT (P < 0.012). APOC3*S1/APOC3*S2 subjects (n = 13) had higher insulin concentrations after the OGTT than APOC3*S1/APOC3*S1 subjects (n = 28) in the 3 periods (diet 1: P < 0.0004; diet 2: P < 0.01; diet 3: P < 0.008). Multiple regression analysis showed that this polymorphism predicted the insulin response to the OGTT (P < 0.031) and the difference between basal insulin concentrations and insulin concentrations after the OGTT (P < 0.002) with the saturated fat diet. In summary, our results suggest that the mutation in the apo C-III gene affects insulin response to an OGTT, which could result in reduced sensitivity to insulin, especially when persons consume diets rich in saturated fat.     

beta-carotene 15,15'-dioxygenase activity and cellular retinol-binding protein type II level are enhanced by dietary unsaturated triacylglycerols in rat intestines

The purpose of this study was to examine effects of dietary triacylglycerols on beta-carotene 15,15'-dioxygenase (EC 1.13.11.21) activity and cellular retinol-binding protein [CRBP (II)] in rats. Six groups of eight rats (7-wk old) were fed one of the following diets: standard (STD; 2.5% soybean oil), saturated (SFA; 15% hydrogenated soybean oil), monounsaturated (MUFA; 15% olive oil), polyunsaturated (PUFA; 15% soybean oil) or clofibrate (CLF; 2.5% soybean oil + 0.2% clofibrate) for 3 wk. The dioxygenase specific activities of the intestinal homogenates in the MUFA and PUFA groups fed the high fat diets were 2.4 times that of the STD group fed a low fat diet (P < 0.01), whereas the activities of the SFA and CLF groups were not significantly different from that of the STD group. The level of CRBP (II) in the intestine of the PUFA group was 1. 3-fold that of the STD group (P < 0.05), whereas there were no significant differences among the other groups. In a second experiment, the dioxygenase activity of rat intestine was followed over 3 wk of feeding the STD and PUFA diets. After the PUFA diet was consumed for 1 d, the activity was enhanced to 2.7 times the baseline level and remained thereafter at that high level, whereas the activity of the STD group remained at the low baseline level. Thus, dietary polyunsaturated triacylglycerols enhanced both beta-carotene 15,15'-dioxygenase activity and CRBP (II) level in rat intestine. These results suggest that the dioxygenase and CRBP (II) are regulated by the same mechanism involving long-chain fatty acids and their metabolites.     

Effects of dietary fat saturation on eicosanoid production, platelet aggregation and blood pressure

The effects of dietary fat saturation on eicosanoid urinary excretion, platelet aggregation (PA) and blood pressure (BP) were studied in 42 healthy subjects. They consumed four consecutive diets differing in their fat saturation [saturated (SFA); monounsaturated (MUFA); polyunsaturated n-6 (PUFA n-6); and polyunsaturated n-6/n-3, (PUFA n-3)]. Each diet period lasted 5 weeks. There were no differences in 24-h 2,3-dinor-6- keto-prostaglandin F1 alpha excretion among dietary periods. A significant effect was noted regarding the excretion of 11-dehydro-thromboxane B2 (P < 0.0001). During the PUFA n-6 phase the excretion was significantly higher than during SFA and MUFA periods. Dietary fatty acid composition had a significant effect on ADP (1 mumolL-1) and collagen (2 mgL-1) induced PA. Dietary fat also had a significant effect on systolic and diastolic blood pressure (P < 0.0001). Both were significantly higher during the SFA period than during the other three periods. Our findings suggest that changes in dietary fatty acids may have mild, but significant, effects on eicosanoid production, platelet aggregation and blood pressure.     

Pulmonary veins: magnetic resonance angiography anatomy

OBJECTIVES: This study was undertaken to investigate the relation between dietary fat composition and adiposity in adult men. SUBJECTS: A sample of 128 male subjects who participated in Phase 2 of the Québec Family Study. DESIGN: The association between adiposity and total dietary fat intake (TFI), saturated fat intake (SFA), monounsaturated fat intake (MUFA) and polyunsaturated fat intake (PUFA) was analyzed in the overall sample. A comparison of body fatness was also performed between consumers of high (4th quartile) and low amounts (1st quartile) of TFI, SFA, MUFA and PUFA. RESULTS: Significant positive correlations were found between the percentage of dietary energy as total fat and body fatness. Men in the upper quartile of TFI displayed significantly more adiposity than those in the lower quartile. Significant differences were also observed when quartiles were established using SFA and MUFA. However, higher intakes of PUFA had no statistical effects on adiposity. CONCLUSION: These results confirm the notion that high fat diets might lead over time to excess body fat deposition. SFA and MUFA intake also seem to be predictors of actual adiposity markers while high PUFA intake seems to exert no effect on these markers.     

Long term metabolic effects of two dietary methods of treating hyperlipidaemia

OBJECTIVES: To compare the long term metabolic effects of two diets for treating hyperlipidaemia. DESIGN: Randomised controlled study: after three weeks of normal (control) diet, subjects were randomly allocated to one of two test diets and followed up for six months. SETTING: Lipid clinic of tertiary referral centre in Naples. SUBJECTS: 63 subjects with primary type IIa and IIb hyperlipoproteinaemia entered the study, and 44 completed it. Exclusion criteria were taking drugs known to influence lipid metabolism, evidence of cardiovascular disease, homozygous familial hypercholesterolaemia, and body mass index over 30. INTERVENTIONS: Two test diets with reduced saturated fat (8%) and cholesterol (approximately 200 mg/day): one was also low in total fat and rich in carbohydrate and fibre, and the other was low in carbohydrate and fibre and rich in polyunsaturated and monounsaturated fats. MAIN OUTCOME MEASURES: Fasting plasma lipid and lipoprotein concentrations; blood glucose, insulin, and triglyceride concentrations before and after a test meal. RESULTS: In comparison with the control diet, both test diets induced significant and similar decreases in low density lipoprotein cholesterol concentrations (by a mean of 0.72 (SE 0.15) mmol/l, P < 0.001, for low total fat diet; by 0.49 (0.18) mmol/l, P < 0.05, for high unsaturated fat diet) and plasma triglyceride concentrations (by 0.21 (0.09) mmol/l, P < 0.05, for low total fat diet; by 0.39 (0.15) mmol/l, P < 0.05, for high unsaturated fat diet), while high density lipoprotein cholesterol concentrations after fasting and plasma glucose and insulin concentrations during test meals were not modified by either diet. CONCLUSIONS: Both test diets are suitable (alone or in combination) for treatment of hypercholesterolaemia.     

Estimates of interdialytic sodium and water intake based on the balance principle: differences between nondiabetic and diabetic subjects on hemodialysis

Whether salt or water intake is the primary cause of interdialytic weight gain (deltaW) has important implication for the design of measures to prevent large deltaW. In 17 hemodialysis patients dialyzed against a bath containing 140 mmol/L of sodium, monthly predialysis serum sodium was compared with post dialysis serum sodium. A decrease in serum sodium in the interdialytic period would indicate that primary water consumption accounts for at least part of the deltaW. Interdialytic sodium intake, isotonic fluid gain (deltaW(isotonic)) and net pure water gain (deltaWH2O) were calculated by balance formulae. Serum sodium concentration was corrected in diabetic subjects to the value corresponding to euglycemia (100 mg/dl). Estimated interdialytic sodium intake was compared with the prescribed sodium intake and, in seven subjects, to sodium intake estimated from dietary records. Results for nondiabetic subjects (N = 9): [Na]post 139.3 +/- 1.9 mmol/L, [Na]pre 140.1 +/- 2.1 mmol/L (NS), deltaW 1.15 +/- 0.55 L/24 hr, deltaW(isotonic) 1.33 +/- 0.57 L/24 hr, deltaWH2O -0.20 +/- 0.58 L/24 hr, estimated sodium intake 206 +/- 75 mmol/24 hr, prescribed sodium intake 121 +/- 29 mmol/24 hr (p = 0.028). Results for diabetic subjects (N = 7): [Na]post 140.1 +/- 2.5 mmol/L, [Na]pre 137.7 +/- 3.1 mmol/L (p < 0.01), deltaW 1.26 +/- 0.38 L/24 hr, deltaW(isotonic) 0.59 +/- 0.63 L/24 hr, deltaWH2O 0.66 +/- 0.39 L/24 hr, estimated sodium intake 160 +/- 81 mmol/24 hr, prescribed sodium intake 124 +/- 30 mmol/24 hr (NS), glycosylated hemoglobin 9.7 +/- 2.8% (normal, 4.1-5.7%). In seven subjects, estimates of sodium intake from balance formulae (233 +/- 113 mmol/24 hr) were not different from estimates from dietary records (212 +/- 87 mmol/24 hr). Sodium intake accounted for all the interdialytic weight gain in nondiabetic subjects. In diabetic patients, only approximately half of the interdialytic weight gain was accounted for by sodium intake. The other half was due to pure water gain, probably caused by hyperglycemia.     

Liquid chromatographic method for analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in milk-based infant formula using matrix solid-phase dispersion

We compared the fasting and postprandial response to a National Cholesterol Education Program (NCEP) II diet with that of a diet high in total (40% of energy) and saturated fat. In free-living conditions, 17 healthy normolipidemic, normoglycemic men and women consumed a high-fat diet, a maintenance diet and the NCEP II diet, for 1 mo each. At the completion of each dietary period, an oral fat load (70 g/m2 body surface area) was administered and plasma triacylglycerol (TAG) determined every 2 h for 8 h. Compared with the high-fat phase, the NCEP II diet was associated with significantly lower energy intake (12.1 +/- 1.1 vs. 7 +/- 0.7 MJ/d) and final body weight (78 +/- 3.8 vs. 76.3 +/- 3.5 kg) (P < 0.01). Plasma high density lipoprotein cholesterol, apolipoprotein (apo) A-I and ApoB concentrations were also significantly lower when subjects consumed the NCEP II diet rather than the high-fat diet (P 相似文献   

Fetal and maternal lipoprotein metabolism in human pregnancy complicated by type I diabetes mellitus

Serum lipid, apolipoprotein concentration, and lipoprotein composition were determined in maternal and umbilical venous cord blood at delivery by elective Cesarean section (CS) in 10 singleton, full-term pregnancies with maternal insulin-dependent diabetes mellitus (type I DM), which predated pregnancy, and in 22 nondiabetic pregnancies. The objectives of the study were to determine the influence of maternal type I DM, and hence potential fetal overnutrition on fetal lipid metabolism. There were no significant differences in gestational age, fetal weight, or fetal serum insulin concentration between the type I DM group and those with nondiabetic pregnancies, although fetal venous cord blood glucose was 3.4 mmol/L (3.0-4.5 mmol/L) (median and 25th-75th percentiles) and 2.9 mmol/L (2.0-3.4 mmol/L), respectively, and maternal Hemoglobin A1c [9.6% (8.2-10.7%) and 6.8% (6.3-7.8%), respectively], was significantly greater in the type I DM subjects (P < 0.02 and 0.002 respectively). Plasma nonesterified fatty acid (NEFA) concentrations were lower in the type I DM mothers [0.85 mmol/L (0.56-2.31 mmol/L) compared with 1.14 mmol/L (0.88-1.24 mmol/L] in nondiabetic pregnancies; P < 0.0001). Serum high-density lipoprotein phospholipids (HDL-PL) were increased in type I DM mothers because of elevated HDL2 phospholipid [0.39 mmol/L (0.27-0.48 mmol/L) compared with 0.12 mmol/L (0.06-0.21 mmol/L), respectively, P < 0.01). The maternal HDL cholesterol (C) concentration was not significantly different in the uncomplicated and type I DM pregnancies. However, in the umbilical venous cord blood, serum levels of NEFA [0.49 mmol/L (0.33-1.29 mmol/L) in type I DM compared with 0.13 mmol/L (0.06-0.33 mmol/L) in nondiabetics; P < 0.02)], total cholesterol (TC) [2.87 mmol/L (1.65-4.86 mmol/L) in type I DM compared with 1.65 mmol/L (1.46-1.87 mmol/L) in nondiabetics; P < 0.02]; free cholesterol (FC) [0.97 mmol/L (0.60-1.26 mmol/L) in type I DM compared with 0.62 mmol/L (0.37-0.75 mmol/L) in nondiabetics; P < 0.05), and cholesteryl ester (CE) [1.90 mmol/L (1.44-3.33 mmol/L) in type I DM compared with 1.01 mmol/L (0.83-1.24 mmol/L) in nondiabetics; P < 0.02), triglyceride (TG) (1.06 [0.50-1.91) mmol/L in type I DM compared with 0.29 [0.25-0.36] mmol/l in nondiabetics; P < 0.001), phospholipid (PL) (2.52 [1.73-3.03) mmol/L in type I DM compared with 1.34 [1.27-1.48] mmol/L in nondiabetics; P < 0.01], and the apolipoproteins A-I and B had significantly higher concentrations in type I DM. In umbilical venous cord blood, ratios of HDL-TC and HDL-PL to apo AI, reflecting the lipid content of HDL, were reduced when the mother had type I DM during pregnancy (P < 0.02 and P < 0.0001, respectively). These results indicate that maternal type I DM may lead to a fetal serum lipoprotein composition more closely resembling that seen in the adult. In type I DM, maternal TG and PL and fetal TC, TG, PL, CE, and FC were correlated to NEFA levels (P < 0.05), but not to glucose, insulin secretion, or maternal control of type I DM. These data suggest that the enhanced supply of NEFA to the fetus in type I DM pregnancies may drive the synthesis of cholesterol as well as TGs and PLs.