Postprandial behavior of plasma squalene and non-cholesterol sterols in men with varying cholesterol absorption.

BACKGROUND: The purpose of this study was to investigate, whether low vs. high absorption of cholesterol affects the postprandial lipid clearance (squalene as the surrogate marker) and postprandial cholesterol metabolism evaluated with plasma levels of cholesterol absorption (cholestanol and plant sterols) and synthesis markers (desmosterol and lathosterol). METHODS: Fifteen normo- or mildly hypercholesterolemic men were divided into low or high cholesterol absorbers on the basis of plasma cholestanol to cholesterol ratio and they volunteered to an oral fat load test containing fat 35 g/m(2) body surface. RESULTS: Plasma squalene to cholesterol ratio did not differ between the groups throughout the postprandial follow-up of 8 h. The level differences in the plasma absorption and synthesis markers seen at baseline remained between the groups, so that in high absorbers the absorption markers remained high and synthesis markers low throughout the postprandial follow-up. The postprandial response curves of desmosterol (p<0.05) and lathosterol (p=0.052) to cholestanol decreased linearly in the low, but not in the high absorbers. CONCLUSIONS: Low vs. high absorption of cholesterol does not affect the first 8-h postprandial lipid clearance. The metabolic profile of cholesterol is maintained postprandially. The postprandial decrease in cholesterol synthesis differs in low vs. high absorbers especially through the desmosterol pathway.

Ester percentages of plant sterols and cholesterol in chylomicrons and VLDL of humans with low and high sterol absorption.

Ester percentages of cholesterol and non-cholesterol sterols were measured in chylomicrons and very low density lipoproteins (VLDL) in 15 subjects. Our hypothesis was that in humans, in contrast to animal experiments, plant sterols in chylomicrons are esterified similarly to cholesterol. In fact, the mean ester percentage of chylomicron sitosterol (approximately 40%), but not of campesterol ( approximately 51%), was lower than that of cholesterol (approximately 54%) in the whole study population. In high cholesterol absorbers (high serum total campesterol, > or = 2.8 mmol/mol of cholesterol), the ester percentages of sitosterol and other non-cholesterol sterols were similar to that of cholesterol in chylomicrons, and the percentages tended to be higher than those in low absorbers. In contrast to chylomicrons, the ester percentages of sterols in VLDL tended to be lower in the high than low absorbers. In conclusion, percentages of plant sterol esters are not consistently lower than those of cholesterol in chylomicrons.

Postprandial responses of individual fatty acids in subjects homozygous for the threonine- or alanine-encoding allele in codon 54 of the intestinal fatty acid binding protein 2 gene.

BACKGROUND: The affinity of intestinal fatty acid binding protein (FABP) for fatty acids is regulated by the polymorphism at codon 54 of the FABP2 gene (alanine-to-threonine shift). We found earlier that the threonine-encoding allele (Thr54) is associated with an increased postprandial lipemic response. OBJECTIVE: We studied the postprandial responses of individual fatty acids in subjects homozygous for the Thr54 or alanine-encoding allele (Ala54). DESIGN: Oral-fat-loading tests were performed in 8 subjects homozygous for Thr54 and in 7 subjects homozygous for Ala54. RESULTS: The postprandial responses of most of the 14-18-carbon fatty acids in chylomicron and VLDL triacylglycerols were significantly elevated in the Thr54 homozygotes whereas the relative increases in these fatty acids were not significantly different in both groups. The amounts of 20- and 22-carbon polyunsaturated fatty acids started to increase later than the amounts of shorter ones after the test meal, and the differences between the groups were mostly insignificant. The responses of chylomicron fatty acids correlated positively with postprandial insulin response in the Thr54 homozygotes and inversely in the Ala54 homozygotes. VLDL fatty acid responses correlated with fasting triacylglycerol concentrations in the Ala54 homozygotes but not in the Thr54 homozygotes. CONCLUSION: The threonine-encoding allele of the FABP2 gene is associated with an increased postprandial response of 14-18-carbon fatty acids but not with changes in the relative amounts of individual fatty acids introduced to chylomicron triacylglycerols.

The effect of orlistat on the fatty acid composition of serum lipid fractions in obese subjects.

OBJECTIVE: To determine whether there are any changes in the fatty acid composition of serum triglycerides, cholesterol esters, and phospholipids induced by administration of orlistat three times a day compared with placebo as combined with a low-fat hypocaloric diet. METHODS: After 4 weeks of placebo administration, 75 obese subjects were randomized to receive either one capsule (120 mg) of orlistat or placebo three times a day with meals for 1 year in conjunction with a nutritionally balanced hypocaloric diet. Food records were kept to estimate the nutrient intake. The fatty acid composition of serum lipids were analyzed with gas chromatograph. The molar percentage proportions of fatty acids in serum lipid fractions were calculated. RESULTS: Compared with placebo, there was a significant decrease in the proportion of linoleic acid in triglycerides, cholesterol esters, and phospholipids in the orlistat group, even after the effect of the decrease in the linoleic acid dietary intake (percent of energy), weight change, and gender were taken into account. However, the use of orlistat explained only 9% to 13% of the decrease in the proportion of linoleic acid in serum cholesterol esters, triglycerides, and phospholipids. CONCLUSION: The long-term treatment with orlistat may result in a small decline in the proportion of diet-derived fatty acids in serum lipid fractions when used in conjunction with low-fat diet.

A high-trans fatty acid diet and insulin sensitivity in young healthy women.

Epidemiological and experimental studies suggest that a diet rich in saturated fat affects insulin sensitivity. Monoenes and dienes that have an usaturated bond with the trans configuration (trans fatty acids) resemble saturated fatty acids with respect to structure, but no published data are available on the effect of trans fatty acids on insulin sensitivity. Therefore, the effects of diets high in trans fatty acids (TFA diet) and oleic acid (monounsaturated fat [MUFA] diet) on glucose and lipid metabolism were studied in 14 healthy women. Subjects consumed both experimental diets for 4 weeks according to a randomized crossover study design. Both experimental diet periods were preceded by consumption of a standardized baseline diet for 2 weeks. The diets provided 36.6% to 37.9% of energy (E%) as fat. In the TFA diet, there was 5.1 E% trans fatty acids, and in the MUFA diet, 5.2 E% oleic acid, substituted for saturated fatty acids in the baseline diet. A frequently sampled intravenous glucose tolerance test (FSIGT) was performed at the end of the experimental diet periods. Glucose effectiveness (S(G)) and the insulin sensitivity index (S(I)) did not differ after the two experimental diet periods. There was also no difference in the acute insulin response between the diets. The total cholesterol to high-density lipoprotein (HDL) cholesterol ratio and serum total triglyceride, HDL, and low-density lipoprotein (LDL) triglyceride and apolipoprotein B (apoB) concentrations were higher (P < .05) after the TFA diet. In conclusion, in young healthy women, the TFA diet resulted in a higher total/HDL cholesterol ratio and an elevation in triglyceride and apo B concentrations but had no effect on glucose and insulin metabolism compared with the MUFA diet.

Divergent incorporation of dietary trans fatty acids in different serum lipid fractions.

Trans fatty acids may be involved in atherosclerotic vascular diseases. We investigated the incorporation of dietary trans fatty acids and oleic acid into the serum triglycerides (TG), cholesterol esters (CE), and phospholipids (PL). Fourteen healthy female volunteers, aged 23.2+/-3.1 yr (mean+/-SD), body mass index 20.8+/-2.1 kg/m2 participated in this study. All subjects consumed both a trans fatty acid-enriched diet (TRANS diet) and an oleic acid-enriched diet (OLEIC diet) for 4 wk according to a randomized crossover design. Both experimental diet periods were preceded by consumption of a baseline diet for 2 wk which supplied 37% of total energy (E%) as fat: 18 E% from saturated fatty acids (SFA), 12 E% from monounsaturated fatty acids, and 6 E% from polyunsaturated fatty acids. Five E% of the SFA in the baseline diet was replaced by trans fatty acids (18:1t and 18:2c,t + 18:2t,t, where c is cis and t is trans) in the TRANS diet and by oleic acid (18:1n-9) in the OLEIC diet. After the TRANS diet, the proportions of 18:1t and 18:2t increased (P<0.001) in all serum lipid fractions analyzed. The increase of 18:1t in TG and PL (1.80+/-0.28 vs. 5.26+/-1.40; 1.07+/-0.34 vs. 3.39+/-0.76 mol% of total fatty acids, respectively) was markedly higher than that in CE (0.44+/-0.07 vs. 0.92+/-0.26), whereas that of 18:2t was nearly the same in all three fractions. The proportions of palmitic, stearic, arachidonic, and eicosapentaenoic acids in TG, CE, and PL and that of oleic acid in TG and CE were decreased when compared with the baseline value. In contrast, the proportion of palmitoleic acid in TG and PL and that of linoleic acid in PL increased on the TRANS diet. After consumption of the OLEIC diet, the proportion of oleic acid increased in all three lipid fractions analyzed, and the percentage increase was nearly the same in all fractions. In contrast, the proportions of 18:1t in TG and PL and 18:2t in TG and CE decreased when compared with the baseline value. In conclusion, a moderate increase in dietary trans fatty acids resulted in a marked incorporation into serum lipids and decreased the conversion of linoleic acid to its more unsaturated long-chain metabolites. Analysis of 18:1t from serum TG and PL seems to reflect reliably the dietary intake of this fatty acid.

Postprandial lipemic response is modified by the polymorphism at codon 54 of the fatty acid-binding protein 2 gene.

Polymorphism of the fatty acid-binding protein 2 (FABP2) gene has been shown to affect the affinity of intestinal FABP for fatty acids. This could cause changes in postprandial triglyceride metabolism. In the present study, postprandial lipemia was studied in normotriglyceridemic subjects with genetic variation in the FABP2 gene. Oral fat-loading tests were performed in 8 subjects homozygous for the Thr-encoding allele at codon 54 of the FABP2 gene and in 7 subjects homozygous for the Ala-encoding allele (wild type). There were no significant differences between these 2 groups in age, body mass index, fasting plasma triglyceride and cholesterol levels, or fasting glucose and insulin levels. The increase of plasma triglyceride concentration after the fat test meal was significantly greater in subjects who were homozygous for the Thr-54 allele (area under the response curve, 4.27+/-1.31 versus 2.49+/-1.18 mmol/L x h-1, P=0.04). The difference was seen in both chylomicron (2.51+/-0. 98 versus 1.41+/-0.74 mmol/L x h-1, P=0.03) and very low-density lipoprotein triglycerides (1.57+/-0.77 versus 0.99+/-0.40 mmol/L x h-1, P=0.04). Postprandial triglyceride response correlated with fasting triglycerides in the Ala-54 homozygotes (r=0.79, P=0.05) but not in the Thr-54 homozygotes (r=0.09), who showed a strong correlation between triglyceride and insulin responses (r=0.83, P=0. 02). With reservations related to a small number of subjects studied, these results indicate that the Thr-encoding allele of the FABP2 gene is associated with increased postprandial lipemia. The lipemic response was associated with postprandial insulin response, suggesting that in the Thr-54 homozygotes, altered postprandial lipemia may also modify insulin action or vice versa.

A high-stearic acid diet does not impair glucose tolerance and insulin sensitivity in healthy women.

Results in epidemiological and experimental studies suggest that a diet rich in saturated fat may affect insulin sensitivity. However, no published data are available on the effect of stearic acid in this respect. Therefore, we examined the effects of a high-stearic acid diet and a high-oleic acid diet on glucose metabolism, serum lipids and lipoproteins, and blood coagulation factors in 15 healthy female subjects. Subjects followed the two experimental diets for 4 weeks according to a randomized crossover design. Both experimental diet periods were preceded by consumption of a baseline diet for 2 weeks. The diets provided 36% of energy (E%) as fat. In the experimental diets, 5 E% stearic or oleic acid was substituted for 5 E% of saturated fatty acids in the baseline diet. After the experimental diets, no differences were found in the insulin sensitivity index (mean+/-SEM, 5.4+/-1.9 v 5.2+/-1.6 x 10(-4) min(-1) x microU(-1) x mL(-1), nonsignificant [NS]), glucose effectiveness (0.026+/-0.006 v 0.026+/-0.003 min(-1), NS), or first-phase insulin reaction ([FPIR] 368+/-57 v 374+/-66 mU/L x min, NS). The concentration of serum lipids and lipoproteins and blood coagulation factors did not differ after the diet periods. In conclusion, a diet rich in stearic acid did not deteriorate glucose tolerance or insulin action in young healthy female subjects as compared with a diet rich in oleic acid.

Incorporation of n-3 fatty acids into plasma lipid fractions, and erythrocyte membranes and platelets during dietary supplementation with fish, fish oil, and docosahexaenoic acid-rich oil among healthy young men.

The effects of n-3 fatty acid supplementation in the form of fresh fish, fish oil, and docosahexaenoic acid (DHA) oil on the fatty acid composition of plasma lipid fractions, and platelets and erythrocyte membranes of young healthy male students were examined. Altogether 59 subjects (aged 19-32 yr, body mass index 16.8-31.3 kg/m2) were randomized into the following diet groups: (i) control group; (ii) fish diet group eating fish meals five times per week [0.38 +/- 0.04 g elcosapentaenoic acid (EPA) and 0.67 +/- 0.09 g DHA per day]; (iii) DHA oil group taking algae-derived DHA oil capsules (1.68 g/d DHA in triglyceride form); and (iv) fish oil group (1.33 g EPA and 0.95 g DHA/d as free fatty acids) for 14 wk. The fatty acid composition of plasma lipids, platelets, and erythrocyte membranes was analyzed by gas chromatography. The subjects kept 4-d food records four times during the study to estimate the intake of nutrients. In the fish diet, in DHA oil, and in fish oil groups, the amounts of n-3 fatty acids increased and those of n-6 fatty acids decreased significantly in plasma lipid fractions and in platelets and erythrocyte membranes. A positive relationship was shown between the total n-3 polyunsaturated fatty acids (PUFA) and EPA and DHA intake and the increase in total n-3 PUFA and EPA and DHA in all lipid fractions analyzed. DHA was preferentially incorporated into phospholipid (PL) and triglyceride (TG) and there was very little uptake in cholesterol ester (CE), while EPA was preferentially incorporated into PL. and CE. The proportion of EPA in plasma lipids and platelets and erythrocyte membranes increased also by DHA supplementation, and the proportion of linoleic acid increased in platelets and erythrocyte membranes in the DHA oil group as well. These results suggest retroconversion of DHA to EPA and that DHA also interferes with linoleic acid metabolism.

Threonine allele in codon 54 of the fatty acid binding protein 2 gene does not modify the fatty acid composition of serum lipids in obese subjects.

Intestinal fatty acid binding protein (I-FABP) participates in the metabolism of fatty acids in the intestinal enterocytes. Threonine encoding allele in codon 54 of the I-FABP gene has been suggested as regulating the absorption of long-chain fatty acids. We examined the fatty acid composition of serum lipid fractions and the concentration of serum free fatty acids after an overnight fast in obese subjects, aged 24-56 years, on their habitual diet. The body mass index of the subjects ranged from 29.7 to 43.3 kg m-2. Six subjects were homozygous for the Thr-54 allele of the I-FABP gene, 37 subjects were heterozygous for the Thr-54/Ala-54 allele and 24 subjects were homozygous for the Ala-54 allele. We did not find any consistent differences in the proportions of long-chain fatty acids in serum triglycerides, cholesterol esters or phospholipids, but the concentration of serum free fatty acids tended to be higher in subjects who were homozygous for the Thr-54 allele (P = 0.13, for trend). In conclusion, our findings suggest that a polymorphism at codon 54 of the I-FABP2 gene does not substantially modify the fatty acid composition of serum lipids in obese Finns.

Fish diet, fish oil and docosahexaenoic acid rich oil lower fasting and postprandial plasma lipid levels.

OBJECTIVE: The present study was carried out to clarify the effects of fish diet, fish oil and docosahexaenoic acid (DHA) rich oil on fasting and postprandial lipid levels in healthy male students. DESIGN: The study was a randomized single-blind study with a control and three study groups. SETTING: The study was carried out in the Departments of Physiology and Clinical Nutrition of University of Kuopio. SUBJECTS: Healthy male volunteers were recruited for the study from the university student population. Fifty-nine subjects entered and 55 completed the study. INTERVENTIONS: For 15 weeks the subjects in the fish diet group ate 4.3 +/- 0.5 fish containing meals per week and those in the fish oil and DHA-oil groups ate 4 g oil per day. Fish diet provided 0.38 +/- 0.04 g eicosapentaenoic acid (EPA) and 0.67 +/- 0.09 g DHA, fish oil 1.33 g EPA and 0.95 g DHA and DHA-oil (EPA-free) 1.68 g DHA per day. RESULTS: Fasting plasma triglyceride levels decreased in all test groups in 14 weeks when compared to the control group (P < 0.05). Total plasma cholesterol levels did not change but the HDL2/HDL3-cholesterol ratio increased in all test groups by over 50% (P < 0.05). The postprandial total and chylomicron triglyceride responses, measured as areas under the response curve, were lowered in 15 weeks by the fish diet and fish oil (P < 0.05), the same tendency (P < 0.1) being seen in DHA-oil group. CONCLUSIONS: These results show that both fasting and postprandial triglyceride concentrations can be decreased with moderate intakes of long-chain n-3 fatty acids either from a fish diet or fish oil and that also pure DHA has a hypotriglyceridemic effect.