Postprandial Hypertriglyceridemia Is Associated with the Variant 54 Threonine FABP2 Gene.

Purpose: Fasting or postprandial hypertriglyceridemia is considered an independent cardiovascular disease (CVD) risk factor. The intestinal fatty acid binding protein (FABP2) is involved in the intracellular transport and metabolism of fatty acids. The presence of the Ala54Thr polymorphism of the FABP2 gene appears to be involved in postprandial hypertriglyceridemia. We explored the possible association of the Ala54Thr polymorphism with fat intolerance in apparently healthy, fasting, normolipidemic subjects with normal body-mass index and without diabetes. Methodology: A total of 158 apparently healthy individuals were classified as fat tolerant (n = 123) or intolerant (n = 35) according to their response (plasma triglycerides) to an oral abbreviated tolerance test with blood samples taken at 0, 2 and 4 h. At 0 h, all subjects ingested 26.3 g of fats. Presence of the Ala54Thr polymorphism of the FABP2 gene was evaluated by polymerase chain reaction⁻restriction fragment length (PCR⁻RFLP). Results: The group with fat intolerance (postprandial hypertriglyceridemia group) showed an increased frequency of the Thr54Thr genotype when compared with the group with normal fat tolerance (control group) (23% vs. 4%, respectively, OR: 16.53, 95% CI: 4.09⁻66.82, p: 0.0001, pc: 0.0003). Carriers of at least one Thr54 allele were up to six times more prevalent in the fat intolerant group than in the non-carriers. (OR: 6.35; 95% CI: 1.86⁻21.59, p: 0.0003, pc: 0.0009). The levels of plasma triglycerides (Tg) at 4 h after the test meal were higher in carriers of at least one 54Thr allele than in carriers of the Ala54 allele (p < 0.05). Conclusions: There is a significant association between postprandial hypertriglyceridemia and the presence of at least one 54Thr allele of the FABP2 gene. In addition, subjects with this genotype showed an increased ratio of Tg/HDL-cholesterol. This parameter is a marker of increased CVD risk and insulin resistance.

Fat Intolerance in Apparently Healthy Individuals with Normal Fasting Lipoproteins Is Associated with Markers of Cardiovascular Risk.

BACKGROUND: Postprandial increase of triglyceride-rich lipoproteins augments the risk of atherosclerotic cardiovascular disease and all-cause mortality. We explored the hypothesis that a simplified oral fat tolerance test can uncover differences in postprandial triglyceride response associated with potentially atherogenic lipoprotein characteristics, even in a cohort of apparently healthy 31-year-old [mean (SD), 31 (11)] nonobese individuals with normal fasting lipids and lipoproteins. METHODS: We used a fat tolerance test in 96 females and 62 males with blood sampled at 0, 2, and 4 h after a breakfast containing 26.3 g of fats. The postprandial triglyceride response was used to classify the individuals in apparently fat-tolerant and apparently fat-intolerant participants. RESULTS: The intolerant individuals were found to have at 0 h significantly higher body mass index, plasma triglycerides, remnant cholesterol, VLDL cholesterol, and LDL cholesterol and lower apolipoprotein (apo) AI and HDL cholesterol than the tolerant individuals. More than 70% of the variability (r2) of the postprandial response in tolerant and intolerant individuals measured as area under the curve or, at a single point at 4 h after the oral fat load, was linearly correlated with 0-h triglycerides (P < 0001). Fasting lipoprotein parameters, proposed to be markers of cardiovascular risk, as the ratios apo B/apo AI, total cholesterol/HDL cholesterol, and triglycerides/HDL cholesterol, were increased in the intolerant individuals. CONCLUSIONS: A simplified oral fat tolerance test, even when used in an apparently healthy, nonobese, normolipidemic cohort, detected that an increased postprandial triglycerides response was associated with augmented lipoprotein markers of increased cardiovascular risk.

Effect of guggulsterone and cembranoids of Commiphora mukul on pancreatic phospholipase A(2): role in hypocholesterolemia.

Guggulsterone (7) and cembranoids (8-12) from Commiphora mukul stem bark resin guggul were shown to be specific modulators of two independent sites that are also modulated by bile salts (1-6) to control cholesterol absorption and catabolism. Guggulsterone (7) antagonized the chenodeoxycholic acid (3)-activated nuclear farnesoid X receptor (FXR), which regulates cholesterol metabolism in the liver. The cembranoids did not show a noticeable effect on FXR, but lowered the cholate (1)-activated rate of human pancreatic IB phospholipase A2 (hPLA2), which controls gastrointestinal absorption of fat and cholesterol. Analysis of the data using a kinetic model has suggested an allosteric mechanism for the rate increase of hPLA2 by cholate and also for the rate-lowering effect by certain bile salts or cembranoids on the cholate-activated hPLA2 hydrolysis of phosphatidylcholine vesicles. The allosteric inhibition of PLA2 by certain bile salts and cembranoids showed some structural specificity. Biophysical studies also showed specific interaction of the bile salts with the interface-bound cholate-activated PLA2. Since cholesterol homeostasis in mammals is regulated by FXR in the liver for metabolism and by PLA2 in the intestine for absorption, modulation of PLA2 and FXR by bile acids and selected guggul components suggests novel possibilities for hypolipidemic and hypocholesterolemic therapies.

Effect of folic acid combined with fluoxetine in patients with major depression on plasma homocysteine and vitamin B12, and serotonin levels in lymphocytes.

OBJECTIVE(S): Folic acid, a micronutrient supporting the natural defense system, may elevate antidepressant responses, although the lymphocyte serotonergic system has not been explored in folate-supplemented depressed patients. METHODS: Twenty-seven patients were randomly assigned to groups receiving fluoxetine (20 mg) and folic acid (10 mg/day) or fluoxetine and placebo for 6 weeks. Clinical outcome was assessed according to the Hamilton Depression Rating Scale (HDRS) at the beginning, during and at the end of treatment. Blood samples were taken, plasma was separated, and lymphocytes were obtained by density gradient centrifugation with Ficoll/Hypaque and differential adhesion to plastic dishes. Fifteen healthy subjects served as controls. Plasma folate, homocysteine and vitamin B12, and serotonin concentration in lymphocytes were determined by HPLC. The HDRS score was significantly lower in patients receiving fluoxetine and folic acid compared with those receiving fluoxetine and placebo after 6 weeks of treatment (7.43 +/- 1.65 vs. 11.43 +/- 1.31, respectively; p = 0.04). Plasma homocysteine statistically significant decreased after folic acid (p = 0.02), but no significant changes were observed in vitamin B12. RESULTS: Serotonin was significantly reduced after fluoxetine either with folate (p = 0.03) or placebo (p = 0.01) probably by the effect of transporter blockade. 5-Hydroxyindoleacetic acid was lower in lymphocytes of patients receiving folate (p = 0.04), indicating a reduced turnover rate, thus accumulating serotonin in the cells. A significant negative correlation was noted between homocysteine and folate. No significant correlations were present among biochemical parameters and depression severity. CONCLUSION: Modifications due to treatment with fluoxetine and folic acid may alter lymphocyte function in depression probably indirectly by reducing homocysteine levels and directly on lymphocytes by modifying the serotonergic system.

Ajoene inhibits both primary tumor growth and metastasis of B16/BL6 melanoma cells in C57BL/6 mice.

Ajoene is an organosulphur compound derived from garlic with important effects on several membrane-associated processes such as platelet aggregation, as well as being cytotoxic for tumor cell lines in vitro. In the present study, we investigated the effect of ajoene on different cell types in vitro, as well as its inhibitory effects on both primary tumors and metastasis in a mouse model. We found ajoene to inhibit tumor cell growth in vitro, but also to inhibit strongly metastasis to lung in the B16/BL6 melanoma tumor model in C57BL/6 mice. As far as we are aware, this is the first report of the anti-metastatic effect of ajoene. Ajoene also inhibited tumor-endothelial cell adhesion, as well as the in vivo TNF-alpha response to lipopolysaccharide. Possible mechanisms of its antitumoral activity are discussed in the light of these results.

[Synergistic antioxidative effect of vitamins E and C on low density lipoproteins from smokers and non-smokers subjects]. / Efecto sinergico antioxidante de las vitaminas E y C sobre la lipoproteina de baja densidad en fumadores y no fumadores.

LDL-lipids peroxidation is an important step in LDL atherogenicity. Tobacco smoke, promotes oxidative stress and reduces LDL-alfa tocoferol content and plasmatic vitamin C concentration. The objective of this double-blind randomized study was to assess the effect of vitamins E and C combined administration, on oxidative susceptibility of LDL isolated from 20 smokers and 10 non-smokers healthy volunteers who received placebo for 15 days and then concomitantly received 400 mg/d vitamin E and 1000 mg/d vitamin C for 30 days. At the end of placebo administration of and vitamins E and C combination; plasma total cholesterol, LDL-C and HDL-C values did not change significantly (p>0.05), plasma triglycerides increased significantly within a normal accepted range (p<0.05) and LDL oxidation susceptibility in smokers decreased by 41,3% and in non-smokers by 54,4% (p<0.05 vs placebo). In conclusion, simultaneous administration of vitamins E and C exerts an important antioxidant effect on LDL-lipids peroxidation. This effect could operate as an attenuating factor of the increased atherogenesis commonly observed in smoker subjects.

Efecto sinérgico antioxidante de las vitaminas E y C sobre la lipoproteína de baja densidad en fumadores y no fumadores / Synergistic antioxidative effect of vitamins E and C on low density lipoproteins from smokers and non-smorkers subjects

La peroxidación de los lípidos de la LDL es un paso importante en la aterogenicidad de esta partícula lipídica, por otra parte el humo del tabaco promueve el stress oxidativo, reduce la concentración endógena de alfa-tocoferol (vitamina E) contenida en la LDL y la concentración de vitamina C del plasma. El objetivo del presente estudio a doble ciego, randomizado fue examinar el efecto de la administración simultánea de las vitaminas E y C sobre la suceptibilidad a la oxidación de la LDL aislada de 20 sujetos fumadores y 10 no fumadores voluntarios, sanos a quienes se administró placebo por 15 días y luego durante 30 días la combinación de vitamina E (400 mg/d) y vitamina C (1000 mg/d). Al final de la administración del placebo y las vitaminas, el colesterol total, LDL-colesterol y HDL-colesterol del plasma no cambiaron significativamente (p>0,05) y los triglicéridos aumentaron significativamente (p<0,05) pero sin sobrepasar el rango normal. La suceptibilidad a la oxidación de la LDL disminuyó 41,3 por ciento en los fumadores y 54,4 por ciento en los no fumadores (p<0,05 vs período pacebo). En conclusión, las vitaminas E y C administradas simultáneamente ejercen un potente efecto antioxidante en la peroxidación de los lípidos de la LDL. Este efecto puede representar un mecanismo atenuador de la aterogénesis incrementada en los sujetos fumadores de cigarrillos

[Changes in of plasma lipoproteins after the use of palm oil in the diet of a group healthy adults]. / Modificaciones de las lipoproteínas del plasma después del uso dietético de la oleína de palma en adultos sanos.

UNLABELLED: Although saturated fat acids have long known to have harmful effects on cholesterol and triacylglycerides levels in blood, new concepts have emerged form recent research on this matter. The purpose of this study was to know the effect of the consumption of palm olein on triacylglycerides and cholesterol levels as well as lipoprotein fractions in the blood plasma of healthy individuals from both sexes. MATERIALS AND METHODS: Different types of fats were administered for 12 weeks to 60 subjects, 45 male, 15 female, between 19 and 45 years of age, who were divided into three groups: the mix group (MG) was administered oil, margarine, and mayonnaise prepared with 50% olein; the olein group (OG) consumed fats prepared with 100% olein; and the control group (CG) consumed regular fats of customary use by the population. The diets provided 25 to 30% of calories. Blood samples were obtained for lipid analysis at the beginning and the end of the study. Plasma triacylglycerides and cholesterol concentrations were determined by means of enzyme and lipoprotein methods (VLDL, LDL; and HDL) by ultracentrifugation. RESULTS AND DISCUSSION: By comparing the groups' means no significant differences were found (p > 0.05) in blood lipids. Individual differences show a slight increase in VLDL-C in OG compared to MG and CG. No differences were found in LDL concentration. CONCLUSIONS: These results contribute evidence to differentiate between the effects of saturated vegetables oils, such as coconut oil, and of palm olein. The authors recommend not extrapolate the effects of type of oil to another in connection with TC increase in blood.

Modificaciones de las lipoproteínas del plasma después del uso dietético de la oleína de palma en adultos sanos / Changes in of plasma lipoproteins after the use of palm oil in the diet of a group healthy adults

Although saturated fat acids have long known to have harmful effects on cholesterol and triacylglycerides levels in blood, new concepts have emerged form recent research on this matter. The purpose of this study was to know the effect of the consumption of palm olein on triacylglycerides and cholesterol levels as well as lipoprotein fractions in the blood plasma of healthy individuals from both sexes. MATERIALS AND METHODS: Different types of fats were administered for 12 weeks to 60 subjects, 45 male, 15 female, between 19 and 45 years of age, who were divided into three groups: the mix group (MG) was administered oil, margarine, and mayonnaise prepared with 50 olein; the olein group (OG) consumed fats prepared with 100 olein; and the control group (CG) consumed regular fats of customary use by the population. The diets provided 25 to 30 of calories. Blood samples were obtained for lipid analysis at the beginning and the end of the study. Plasma triacylglycerides and cholesterol concentrations were determined by means of enzyme and lipoprotein methods (VLDL, LDL; and HDL) by ultracentrifugation. RESULTS AND DISCUSSION: By comparing the groups' means no significant differences were found (p > 0.05) in blood lipids. Individual differences show a slight increase in VLDL-C in OG compared to MG and CG. No differences were found in LDL concentration. CONCLUSIONS: These results contribute evidence to differentiate between the effects of saturated vegetables oils, such as coconut oil, and of palm olein. The authors recommend not extrapolate the effects of type of oil to another in connection with TC increase in blood.