LDL particle size and LDL and HDL cholesterol changes with dietary fat and cholesterol in healthy subjects

We have conducted a dietary trial in 54 men and 51 women with a wide range of fasting cholesterol values to examine the use of low density lipoprotein (LDL) particle size to predict the lipoprotein response to dietary fat and cholesterol. After a 2-week low fat period, subjects were given two liquid supplements in addition to their low fat diet for 3 weeks each, one containing 31-40 g of fat and 650-845 mg of cholesterol, the other fat free. LDL particle type was determined by 3-15% gradient gel electrophoresis. On multiple regression, LDL type was independently related to plasma triglyceride (P < 0.001), waist circumference (P < 0.01), and high density lipoprotein (HDL) (P < 0.001) accounting for 56% of the variance in LDL type in the whole group. Change in LDL cholesterol with dietary fat and cholesterol was unrelated to LDL particle size in either men or women. However, change in HDL cholesterol in men was strongly related to LDL particle type (r = -0.52, P = 0.001) and change in HDL2 cholesterol in women was related to LDL particle type (r = -0.40, P < 0.01). In conclusion, we are unable to confirm the finding that LDL particle type can predict changes in LDL cholesterol following changes in dietary fat intake. However, LDL particle type can independently predict changes in HDL cholesterol in men and accounts for 27% of the variance.     

Increases in dietary cholesterol and fat raise levels of apoprotein E-containing lipoproteins in the plasma of man

Previous studies from this laboratory have determined that diets containing the usual amounts of fat to which are added 750-1500 mg/day cholesterol elevate the plasma cholesterol concentration by variable amounts, depending upon the ratio of polyunsaturated to saturated fatty acids (P/S ratio) of the diet. Diets with P/S ratios of 0.25-0.4 are accompanied by elevations of low density lipoprotein (LDL) cholesterol, whereas diets with a P/S ratio of 2.5 produce no significant changes in cholesterol levels. On the low P/S ratio diets, the structure, composition, and interaction with cultured fibroblasts of LDL are not significantly changed. Plasma high density lipoprotein (HDL) cholesterol levels remain constant, but HDL2 increase relative to HDL3. In the present study, not only dietary cholesterol but also total dietary fat was altered. Six normal young men were fed a basal diet consisting of 18% protein, 51% carbohydrate, and 30% fat, containing 250 mg/day cholesterol. After 2 weeks, an experimental diet consisting of 18% protein, 42% carbohydrate, and 39% fat, containing 1760 mg/day cholesterol, was fed for 4 weeks. The P/S ratios of both diets were about 0.4. Plasma samples were taken twice during each dietary period from 12- to 14-h-fasted subjects and analyzed for their contents of lipoprotein lipids. Plasma levels of LDL and HDL cholesterol increased by 30 and 13 mg/dl, respectively; total and very low density lipoprotein (VLDL) triglyceride concentrations were unaltered. The plasma concentrations of apoproteins (apo) B, E. and A-I, but not A-II, were elevated. Plasma samples also were studied by zonal ultracentrifugation, gel permeation column chromatography, and Pevikon electrophoresis. Although on zonal ultracentrifugation the total concentrations of LDL were increased, the flotation properties and chemical compositions of LDL were not changed. By contrast, HDL2 and HDL3L concentrations increased, and HDL2 became enriched with cholesteryl esters. On gel permeation chromatography, with the subjects on the basal diet, plasma cholesterol eluted in two peaks, corresponding to LDL and HDL. The sizes of the peaks increased on the experimental diet. ApoE eluted in two peaks: one at the leading edge of LDL (corresponding to VLDL or IDL) and the other in the area between LDL and HDL, corresponding to HDLC. On the experimental diet, the apoE peak between LDL and HDL increased. On Pevikon electrophoresis apoE migrated between the LDL and HDL bands. This apoE peak was increased on the experimental diet. These findings suggest that increasing the concentrations of both dietary cholesterol and total fat can increase the levels of plasma LDL, HDL2, and HDLC in fasting normal subjects. Thus, the concentrations of some putatively atherogenic as well as antiatherogenic lipoproteins increased in plasma, and the apparent paradox between the epidemiological and metabolic behaviors of some lipoproteins remains. Clearly, more work is needed to resolve the roles of various lipoproteins in plasma in atherosclerosis.     

Strobilurin M, tetrachloropyrocatechol and tetrachloropyrocatechol methyl ether: new antibiotics from a Mycena species

OBJECTIVE: To describe lipid and lipoprotein perturbations in gestational diabetes mellitus (GDM) and to examine the potential consequences--e.g, increased birth weight and increased placental lipid transfer. STUDY DESIGN: Maternal and cord free fatty acids (FFAs) and total, very low density lipoprotein (VLDL), low density lipoprotein (LDL), high density lipoprotein (HDL) (and maternal HDL2 and HDL3), triglyceride (TG), and cholesterol and dietary intake were determined for women with diet-treated GDM and for healthy pregnant women with normal glucose tolerance. RESULTS: Women with GDM had higher hemoglobin A1c than controls, while body weight gain was significantly lower for women with GDM as compared to controls. Plasma and lipoprotein TG concentrations were greater for women with GDM, and although plasma FFAs were higher in women with GDM versus controls, the difference was not significant. No differences were observed between groups with respect to maternal plasma or lipoprotein cholesterol. Cord plasma and lipoprotein lipids were similar between groups; with the exception of VLDL + LDL TG, which was lower in women with GDM. In controls, there were significant correlations between maternal plasma TG and cord FFAs; maternal HDL2 cholesterol and cord plasma cholesterol; and maternal plasma TG, maternal HDL2 cholesterol, cord FFAs, and infant birth weight. In GDM, maternal plasma cholesterol and cord VLDL + LDL cholesterol correlated. There were no significant correlations between maternal or cord lipids and infant birth weight in women with GDM. CONCLUSION: Hypertriglyceridemia, rather than hypercholesterolemia, is a feature of GDM. However, elevations in maternal plasma and lipoprotein TGs in women with GDM were not related to fetal lipid concentrations or infant birth weight.     

The nature of the association between diet and serum lipids in the community: A twin study.

Diet is commonly thought to be an environmental influence on serum lipid concentrations. This study evaluated whether total caloric and fat intake predict total cholesterol (TC), low-density lipoprotein cholesterol (LDL), high-density lipoprotein cholesterol (HDL), and triglyceride (TRIG) concentrations for environmental, as compared with genetic, reasons among 137 monozygotic and 67 dizygotic young adult twins. When genetic influences were controlled by correlating differences between monozygotic co-twins, a significant association remained between diet and TC, LDL, and HDL, suggesting that these dietary and serum lipid measures correlate for environmental reasons. Twin structural equation modeling confirmed these results. Overall, these results provide additional support for the hypothesis that diet is an environmental influence on TC, LDL, and HDL. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Insulin sensitivity in familial hypercholesterolemia

Insulin resistance is found in association with obesity, non-insulin-dependent diabetes mellitus, and essential hypertension, which are all risk factors for atherosclerotic cardiovascular disease. Furthermore, hyperinsulinemia has been reported in familial combined hyperlipoproteinemia and endogenous hypertriglyceridemia. Finally, relatively high serum triglyceride and low high-density lipoprotein (HDL) cholesterol concentrations invariably accompany hyperinsulinemia. Whether insulin sensitivity is affected by the isolated presence of high levels of serum low-density lipoprotein (LDL) cholesterol has not been clearly established. We studied 13 subjects with heterozygous familial hypercholesterolemia (FHC) and 15 normocholesterolemic subjects selected to be free of any other known cause of insulin resistance. Thus FHC patients and controls had normal body weight and fat distribution, glucose tolerance, blood pressure, and serum triglyceride and HDL cholesterol concentrations, but were completely separated on plasma LDL cholesterol concentrations (6.05 +/- 0.38 v 3.27 +/- 0.15 mmol/L, P < .0001). Fasting plasma levels of glucose, insulin, free fatty acids (FFA), and potassium and fasting rates of net carbohydrate and lipid oxidation were superimposable in the two study groups. During a 2-hour euglycemic (approximately 5 mmol/L) hyperinsulinemic (approximately 340 pmol/L) clamp, whole-body glucose disposal rates averaged 30.4 +/- 2.3 and 31.1 +/- 3.0 mumol.kg-1 x min-1 in FHC and control subjects, respectively (P = 0.88). The ability of exogenous hyperinsulinemia to stimulate carbohydrate oxidation and energy expenditure and suppress lipid oxidation and plasma FFA and potassium levels was equivalent in FHC and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of a low-fat, high-carbohydrate diet on serum high density lipoprotein cholesterol and triglyceride

OBJECTIVE: To determine whether substituting carbohydrate for saturated fat has any adverse effects on serum high density lipoprotein (HDL) cholesterol and triglycerides in free-living individuals. DESIGN: Randomised crossover trial. SETTING: General community. SUBJECTS: Volunteer sample of 38 healthy free-living men with mean (s.d.) age 37 (7) y, moderately elevated serum total cholesterol 5.51 (0.93) mmol/l and body mass index 26.0 (3.6) kg/m2. INTERVENTIONS: Participants completed two six week experimental periods during which they consumed either a traditional Western diet (36%, 18%, and 43% energy from total, saturated, and carbohydrate, respectively) or a low-saturated fat high-carbohydrate diet (22%, 6% and 59% energy from total, saturated, and carbohydrate, respectively). Dietary principles were reinforced regularly, but food choices were self-selected during each experimental period. MAIN OUTCOME MEASURES: Serum lipids, body weight and plasma fatty acids. RESULTS: Reported energy and nutrient intakes, plasma fatty acids, and a drop in weight from 79.1 (12.5) kg on the Western diet to 77.6 (12.0) kg on the high-carbohydrate diet (P < 0.001) confirmed a high level of compliance with experimental diets. Total and low density lipoprotein (LDL) cholesterol fell from 5.52 (1.04) mmol/l and 3.64 (0.88) mmol/l, respectively on the Western diet to 4.76 (1.10) mmol/l and 2.97 (0.94) mmol/l on the high-carbohydrate diet (P < 0.001). HDL cholesterol fell from 1.21 (0.27) mmol/l on the Western diet to 1.07 (0.23) mmol/l on the high-carbohydrate diet (P = 0.057), but the LDL:HDL cholesterol ratio improved from 3.17 (1.05) on the Western diet to 2.88 (0.97) on the high-carbohydrate diet (P = 0.004). Fasting triglyceride levels were unchanged throughout the study. CONCLUSIONS: Replacement of saturated fat with carbohydrate from grains, vegetables, legumes, and fruit reduces total and LDL cholesterol with only a minor effect on HDL cholesterol and triglyceride. It seems that when free living individuals change to a fibre rich high-carbohydrate diet appropriate food choices lead to a modest weight reduction. This may explain why the marked elevation of triglyceride and reduction of HDL cholesterol observed on strictly controlled high-carbohydrate diets may not occur when such diets are followed in practice.     

Diet, plasma lipoproteins and experimental atherosclerosis in baboons (Papio sp.)

Diet-induced hyperlipidaemia in baboons is similar to that in humans. As in humans, the ratio between low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol is a major determinant of atherosclerosis. Baboons, like humans and other non-human primates, vary in their lipaemic responses to dietary lipids. By selective breeding based on variability in plasma and lipoprotein cholesterol response to diet, lines of baboons with high and low responses of various lipoproteins have been developed. Genetic analyses suggest that lipoprotein patterns in response to dietary cholesterol and fat are heritable. Metabolic and molecular studies of high and low LDL and HDL cholesterol responses to dietary lipids have suggested that different mechanisms regulate plasma LDL cholesterol on the chow and on the high cholesterol-high fat (HCHF) diet. On the chow diet, plasma LDL cholesterol levels are positively associated with cholesterol absorption and negatively associated with hepatic LDL receptor levels and, thus, cholesterol absorption and LDL receptors seem to regulate plasma LDL cholesterol levels. However, when the animals consume a human-like fat- and cholesterol-enriched diet, plasma LDL cholesterol levels are not associated with either cholesterol absorption or hepatic LDL receptor mRNA levels, but are negatively associated with plasma 27-hydroxycholesterol concentrations, hepatic sterol 27-hydroxylase activity, and mRNA levels. Hepatic sterol 27-hydroxylase activity and mRNA levels are induced by dietary cholesterol and fat in low responding baboons more than in high responding baboons. Thus, the ability to induce sterol 27-hydroxylase determines the LDL cholesterol response in baboons. High HDL response baboons often have high levels of HDL1 in their plasma. Our studies suggest that the N-terminal fragment of apo C-I with 38 amino acids and a molecular weight of approximately 4 kDa acts as a cholesteryl ester transfer inhibitor peptide in high HDL1 baboons. The inhibitor peptide associates with apo A-1 in HDL to produce a modified apo A-1 protein with a molecular weight of approximately 31 kDa. The inhibitor peptide is a gene product and the presence of this peptide produces an antiatherogenic high HDL1 phenotype.     

Relationships between dietary fat, body fat, and serum lipid profile in prepubertal children

OBJECTIVE: The purpose of the study was to test the hypothesis that dietary fat components were associated with the serum lipid profile independent of ethnicity, body fat, and fat distribution in prepubertal children. RESEARCH METHODS AND PROCEDURES: Sixty-six children (45 African American and 21 Caucasian), aged from 4 to 10 years, were recruited into the study. Dietary total fat, saturated fat, monounsaturated fat, and polyunsaturated fat were estimated by averaging two 24-hour diet recalls. Fasting serum triacylglycerol, total cholesterol, and high-density lipoprotein cholesterol were analyzed, and low-density lipoprotein cholesterol (LDL-C) was calculated by the method of Friedewald. Body composition and fat distribution were measured by dual energy X-ray absorptiometry and computed tomography. RESULTS: Children in both ethnic groups tended to overreport their dietary intake relative to total energy expenditure by 18%. African American children consumed more energy from total fat (35.3% vs. 31.5%, p<0.05), saturated fat (13.7% vs 12.2%, p<0.05), protein (16.4% vs. 13.2%, p=0.02), and less from carbohydrate (48% vs. 57.1%, p<0.01) than Caucasian children. There was no significant correlation between dietary fat and either serum lipids or body fat indices after adjusting for nonfat energy intake and total lean tissue mass. Total body fat (r=0.32), subcutaneous abdominal adipose tissue (r=0.39), and intra-abdominal adipose tissue (r=0.42) were positively related to serum triacylglycerol; these associations remained significant in a multiple linear regression model in which body fat indices were adjusted for ethnicity, total lean tissue, dietary total fat, and nonfat intake. DISCUSSION: Our results do not support a link between dietary fat and serum lipids; instead, our data suggest that body fat may play a more important role than dietary fat in the course of cardiovascular disease development in prepubertal children.     

Dietary cholesterol affects serum lipids, lipoproteins and LDL metabolism in cynomolgus monkeys in a dose-dependent manner

To examine the mechanism(s) underlying the cholesterolemic response to dietary cholesterol and saturated fatty acids, low density lipoprotein (LDL) metabolism was studied in two groups of cynomolgus monkeys fed diets containing 30 or 36% of total energy as fat. At each dietary fat level, the same group of monkeys was sequentially fed three dietary cholesterol concentrations as egg yolk in the following sequence: low (0.01 mg/kJ), medium (0.03 mg/kJ) and high (0.05 mg/kJ) for 30, 32 and 24 wk, respectively. Dietary polyunsaturated and monounsaturated fatty acids were the same in the two groups; the 6% difference in fat was due to the saturated fatty acids, 12:0 and 14:0. Serum total cholesterol, LDL cholesterol and LDL apolipoprotein B concentrations increased (P < 0.05) with dietary cholesterol in a dose-dependent manner in both fat groups. These elevations were the result of generally increasing LDL apolipoprotein B production rates, concomitant with reduced LDL apolipoprotein B fractional clearance at the high cholesterol intake. Serum HDL cholesterol and HDL apolipoprotein A-I concentrations were not affected in a consistent manner. These results demonstrate that cynomolgus monkeys are hyperresponsive to dietary cholesterol compared with humans, suggesting that this model may be useful in identifying metabolic and genetic predictors for hyperresponsiveness to dietary cholesterol in humans as well as assessing the metabolic heterogeneity of responses to dietary cholesterol.     

Dietary fat type and energy restriction interactively influence plasma leptin concentration in rats

To investigate whether dietary fat source and energy restriction interactively influence plasma leptin levels and its association of leptin with insulin action, rats were fed diets containing either fish, safflower oil, or beef tallow (20% wt/wt) for 10 weeks. Groups of rats consumed each diet ad libitum or at 85% or 70% of ad libitum energy intake in a design that held fat intake constant. Graded levels of energy restriction caused body weight to decrease (P < 0.001) differently according to the dietary fat provided. Plasma leptin concentrations were 60% higher (P < 0.05) in the groups fed fish oil and safflower oil ad libitum compared with those in the beef tallow group, despite smaller perirenal fat mass and fat cell size in the fish oil-fed animals. Energy restriction resulted in a 62% decrease (P < 0.05) in leptin levels in fish oil- and safflower oil-fed rats, whereas no changes were observed in beef tallow-fed animals. Plasma insulin levels were lower (P < 0.05) in the fish oil group fed ad libitum compared with those in the two other diet groups. These data demonstrate a hyperleptinemic effect in animals consuming diets rich in polyunsaturated fatty acid, which can be normalized to the level of saturated fat consumption by mild energy restriction. Thus, dietary fatty acid composition, independent of adipose tissue mass, is an important determinant of circulating leptin level in diet-induced obesity.     

U-shape relationship between change in dietary cholesterol absorption and plasma lipoprotein responsiveness and evidence for extreme interindividual variation in dietary cholesterol absorption in humans

A possible relationship between change in dietary cholesterol absorption and plasma lipoprotein responsiveness was examined in 18 normal subjects fed low fat low cholesterol, high fat low cholesterol, and high fat high cholesterol diets. For the group, neither dietary cholesterol nor dietary fat affected the percentage dietary cholesterol absorption, whereas dietary cholesterol intake raised total and LDL-C and dietary fat raised total, LDL, and HDL-C. On a fixed diet there was approximately a 2-fold variation among subjects in percentage dietary cholesterol absorption. Subjects also varied in response to dietary cholesterol and fat with regard to dietary cholesterol absorption and plasma lipoprotein responsiveness. There was a U-shaped parabolic relationship between dietary cholesterol-induced percent change in LDL-C and the change in percentage dietary cholesterol absorption (R2 = 0.62, P = 0.005). A similar but weaker relationship characterized the responsiveness of HDL-C (R2 = 0.38, P = 0.05). For the group, increased cholesterol intake raised dietary cholesterol mass absorption from 1.6 to 4.6 mg/kg per day, but the range of increase was from 1 to 4.7 mg/kg per day. Increased fat intake also affected dietary cholesterol mass absorption with most subjects displaying a strong inverse relationship between fat intake and mass absorption (r = -0.77, P < 0.003). In summary: i) the percentage change in dietary cholesterol absorption in response to dietary cholesterol does appear to regulate diet responsiveness of LDL and HDL-C, and ii) the large variability in percent absorption and changes in percentage and mass absorption in response to dietary cholesterol suggest the presence of genetically determined differences among individuals in the regulation of dietary cholesterol absorption.     

Less fat or a different fat?

Current dietary advice with a view to avoiding cardiovascular pathology is to replace fatty foodstuffs and those rich in saturated fat and cholesterol by food rich in complex carbohydrates. Although substitution of carbohydrates for fat lowers the blood level of low-density lipoprotein (LDL) cholesterol, it also lowers the level of high-density lipoprotein (HDL) cholesterol, thereby adversely influencing the risk profile for cardiovascular disease. Neither does a low fat diet appear to reduce obesity, another risk factor. A modern advice based on published research reads: obese persons should reduce their intake of saturated and trans-fatty acids by lowering the consumption of dairy fat, meat and hardened oils (bakery products and catering products fried in hardened fats), and in addition should consume less products with added sugars and refined starch. Carbohydrates should be provided by fruits, vegetables, leguminous plants and whole-wheat products. Persons of about the ideal weight should replace saturated and trans-fatty acids in their diet by unsaturated plant oils, and products with refined carbohydrates by fruits, vegetables and whole-wheat products.     

Low linolenate and commercial soybean oils diminish serum HDL cholesterol in young free-living adult females

OBJECTIVE: A mutant soybean line (A16) low in linolenic acid content (2% of oil by weight) was developed to increase oil oxidative stability. It was unknown whether serum lipid and lipoprotein concentrations in humans would be affected should A16 soybean oil (A16 oil) replace commercial soybean oil in diets. This study was conducted to examine the hypothesis that in free-living normolipidemic women, the consumption of A16 oil at approximately 10% of energy intake (en%) would not affect serum lipids and lipoproteins differently than would the consumption of the same amount of a commercial soybean oil with 7% of linolenic acid content. DESIGN: Fifteen free-living female college students consumed the soybean oil daily with regular meals for 9 weeks in different orders, with each test oil being eaten for 3 weeks. During the study, 13 en% was provided by each test oil and a total of 35 en% was from dietary fat. Serum concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), low-density lipoprotein cholesterol (LDL cholesterol) and triacylglycerides (TAG) were measured. Serum total fatty acid patterns were analyzed as well. RESULTS: Each of the three test oils decreased serum total cholesterol, LDL cholesterol and TAG concentrations from the baseline values. The feeding of A16 and commercial soybean oils decreased serum HDL cholesterol significantly compared with coconut oil (p < 0.05). Dietary inclusion of coconut oil increased serum myristic acid significantly more than did either soybean oil (p < 0.01). Serum arachidonic acid concentrations were significantly greater with A16 consumption than with commercial soybean oil consumption (p < 0.001). CONCLUSION: A16 and commercial soybean oils both diminished serum HDL cholesterol. Although the fatty acid composition differed between the two soybean oils, A16 oil and commercial oil had similar effects on serum concentrations of lipoproteins and lipids. With increased oxidative stability, A16 oil is a good alternative to commercial soybean oil.     

Cholesteryl ester transfer protein gene polymorphism is a determinant of HDL cholesterol and of the lipoprotein response to a lipid-lowering diet in type 1 diabetes

The TaqIB cholesteryl ester transfer protein (CETP) gene polymorphism (B1B2) is a determinant of HDL cholesterol in nondiabetic populations. Remarkably, this gene effect appears to be modified by environmental factors. We evaluated the effect of this polymorphism on HDL cholesterol levels and on the lipoprotein response to a linoleic acid-enriched, low-cholesterol diet in patients with type 1 diabetes. In 44 consecutive type 1 diabetic patients (35 men), CETP polymorphism, apolipoprotein (apo) E genotype, serum lipoproteins, serum CETP activity (measured with an exogenous substrate assay, n = 30), clinical variables, and a diet history were documented. The 1-year response to diet was assessed in 14 type 1 diabetic patients, including 6 B1B1 and 6 B1B2 individuals. HDL cholesterol was higher in 10 B2B2 than in 14 B1B1 homozygotes (1.63 +/- 0.38 vs. 1.24 +/- 0.23 mmol/l, P < 0.01). HDL cholesterol, adjusted for triglycerides and smoking, was 0.19 mmol/l higher for each B2 allele present. CETP activity levels were not significantly different between CETP genotypes. Multiple regression analysis showed that VLDL + LDL cholesterol was associated with dietary polyunsaturated:saturated fatty acids ratio (P < 0.02) and total fat intake (P < 0.05) in the B1B1 homozygotes only and tended to be related to the presence of the apo E4 allele (P < 0.10). In response to diet, VLDL + LDL cholesterol fell (P < 0.05) and HDL cholesterol remained unchanged in 6 B1B1 homozygotes. In contrast, VLDL + LDL cholesterol was unaltered and HDL cholesterol decreased (P < 0.05) in 6 B1B2 heterozygotes (P < 0.05 for difference in change in VLDL + LDL/HDL cholesterol ratio). This difference in response was unrelated to the apo E genotype. Thus, the TaqIB CETP gene polymorphism is a strong determinant of HDL cholesterol in type 1 diabetes. This gene effect is unlikely to be explained by a major influence on the serum level of CETP activity, as an indirect measure of CETP mass. Our preliminary data suggest that this polymorphism may be a marker of the lipoprotein response to dietary intervention.     

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 dietary fat reduction and increased aerobic exercise on cardiovascular risk factors

1. The combined effect of dietary fat reduction and increased aerobic exercise on coronary heart disease (CHD) risk factors was investigated in healthy, normolipidaemic, normotensive, sedentary individuals. 2. After a baseline period of 2 weeks, 21 subjects were randomly allocated to one of two intervention groups (low fat exercise (LFEX) or low fat control (LFC)) for 8 weeks. Both groups were counselled to reduce their dietary fat intake to 20-25% energy from fat. The LFEX group was also required to commence an aerobic exercise programme (4 x 45 min per week). 3. In both groups, the falls in total cholesterol seen at week 4 were not maintained at the end of the study; however, the LFEX group maintained a fall in low-density lipoprotein (LDL) of 0.21 +/- 0.11 mmol/L. At the end of the study, the LFC group experienced a fall in high-density lipoprotein (HDL)-cholesterol of 0.16 +/- 0.05 mmol/L, due to a 0.19 +/- 0.07 mmol/L fall in the HDL2 subfraction. The LFEX group experienced no change in HDL (-0.09 +/- 0.06 mmol/L) or HDL2 (-0.09 +/- 0.05 mmol/L). 4. At the end of the study the LFEX and LFC groups experienced a 7 +/- 3 and 5 +/- 1 mmHg fall in systolic blood pressure, respectively, while the LFEX group also observed a 4 +/- 2 mmHg fall in diastolic blood pressure. 5. The benefits of a low-fat diet combined with aerobic exercise include a reduction in LDL and blood pressure, while maintaining HDL through the HDL2 subfraction.     

Dietary fat saturation and chain length modulate guinea pig hepatic cholesterol metabolism

The effects of dietary fat saturation and saturated fatty acid composition on plasma lipoprotein concentrations and hepatic cholesterol metabolism were investigated in guinea pigs. Animals were fed semipurified diets containing 15 g fat/100 g diet, as palm kernel, palm oil, beef tallow, lard, olive oil or corn oil. Plasma lipoprotein concentrations were significantly altered by the type of dietary fat. The LDL cholesterol concentration was highest in animals fed the diet with palm kernel and lowest in animals fed the diet with corn oil, whereas HDL cholesterol was lowest in beef tallow-fed guinea pigs (P < 0.01). Hepatic cholesteryl ester concentrations were 100% higher in animals fed diets containing polyunsaturated corn oil and monounsaturated olive oil compared with animals fed any of the saturated fat diets (P < 0.01). Hepatic 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity varied in the different dietary fat groups independent of hepatic cholesterol pools or plasma LDL concentrations. In contrast, hepatic acyl-CoA: cholesterol acyltransferase (ACAT) activity was significantly correlated with plasma LDL cholesterol across all dietary groups (r = 0.63, P < 0.001). These data demonstrate that regulation of hepatic HMG-CoA reductase activity is relatively independent of changes in plasma lipoprotein levels, whereas hepatic ACAT activity exhibits a positive correlation with plasma LDL cholesterol concentrations.     

Skeletal muscle metabolic characteristics before and after energy restriction in human obesity: fibre type, enzymatic beta-oxidative capacity and fatty acid-binding protein content

BACKGROUND: Skeletal muscle has the ability to adapt as result of dietary, hormonal or pharmacological interventions affecting energy metabolism. The aim of the present study was to investigate the effects of energy restriction on skeletal muscle metabolic characteristics in obese women. METHODS: The effects of 8 weeks' energy restriction on body composition, energy expenditure and skeletal muscle characteristics were investigated in 28 healthy obese women. Subjects were aged 37.9 +/- 1.5 years and had a body mass index of 32.0 +/- 0.8 kg m-2. RESULTS: Energy restriction (2800 kJ day-1) resulted in a 10.8 +/- 0.5 kg weight loss consisting of 8. 6 +/- 0.5 kg of fat mass and 2.2 +/- 0.3 kg of fat-free mass. Basal respiratory exchange ratio, sleeping metabolic rate and exercise-induced thermogenesis significantly declined in response to the diet. These changes were accompanied by an increase (P = 0.038) in the skeletal muscle content of cytosolic fatty acid-binding protein (H-FABP), whereas no changes occurred in fibre type distribution or activities of enzymes reflecting beta-oxidation and mitochondrial density (3-hydroxyacyl-CoA dehydrogenase and citrate synthase respectively). CONCLUSION: The results suggest that increased capacity of intracellular fatty acid transport in skeletal muscle cells is involved in the physiological adaptations of fat metabolism to energy restriction in obese female subjects.     

Epidemiology and treatment of otitis media with effusion in children in the first year of primary school

Children with acute lymphoblastic leukaemia (ALL) typically gain weight at excessive rates during and after therapy, and a high proportion of young adult survivors are obese. Previous studies have failed to identify the abnormalities in energy balance that predispose these children to obesity. The aim of this study was to determine the cause of excess weight gain in children treated for ALL by testing the hypothesis that energy expenditure is reduced in these patients. Twenty children [9 boys, 11 girls; mean age 10.9 (3.2) y] treated for ALL who had shown excess weight gain, but were not obese [mean body mass index SD score 0.70 (1.04)], were closely and individually matched with 20 healthy control children [9 boys, 11 girls; mean age 10.7 (3.0) y; mean body mass index SD score 0.27 (0.91)]. In each child we measured total energy expenditure by doubly-labeled water method, resting energy expenditure, energy expended on habitual physical activity, and energy intake. Total energy expenditure was significantly higher in control subjects than in patients: mean paired difference 1185 kJ/d (282 kcal/d), 95% confidence interval (CI) 218-2152. This difference was largely due to reduced energy expended on habitual physical activity in the patients. Resting energy expenditure was lower in the patients: mean paired difference 321 kJ/d (76 kcal/d), 95% CI 100-541. Energy intake was also lower in the patients: mean paired difference 1001 kJ/d (238 kcal/d), 95% CI 93-1909. Children treated for ALL are predisposed to excess weight gain, and subsequently obesity, by reduced total energy expenditure secondary to reduced habitual physical activity. Prevention of obesity in ALL should focus on modest increases in habitual physical activity, modest restriction of dietary intake, and monitoring of excess weight gain.     

Pathophysiology of carbohydrate-deficient glycoprotein syndrome--neuroradiological and neurophysiological study

We examined the cross-sectional relation of dietary vitamin C intake to serum lipids in 1,825 preadolescent black and white girls. Dietary vitamin C intake exclusive of supplement use, determined by 3-day diet record, appeared unrelated to total serum cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglyceride levels. Because other investigators have demonstrated an inverse association between vitamin C and total serum cholesterol in individuals with elevated total serum cholesterol levels, we analyzed the subgroup of 285 girls (142 blacks and 143 whites) with total serum cholesterol levels > or = 200 mg per dl. Multivariate analyses of this subgroup, which adjusted for saturated fat, polyunsaturated fat, monounsaturated fat, cholesterol, fiber, and energy intake and for body mass index, demonstrated negative association between vitamin C intake and total serum cholesterol. In girls with total serum cholesterol levels > or = 200 mg per dl, each 100 mg per day increase in dietary vitamin C intake (ranges 13-373 and 14-242 mg per day for blacks and whites, respectively) was associated with a total serum cholesterol decrease of 4 mg per dl (95% confidence limits = -10.34, 2.77) in blacks and 13 mg per dl (95% confidence limits = -22.99, -2.68) in whites. If the observed association is causal and generalizable, our results suggest that increased vitamin C intake could play an important role in the cholesterol homeostasis of females with elevated total cholesterol levels.