The Journal of Nutritional Biochemistry

2010-09-01

Mechanisms underlying the cardioprotective effects of omega-3 polyunsaturated fatty acids

Yuriko Adkins, Darshan S. Kelley — 2010-04-12

Abstract: Typical omega 3 polyunsaturated fatty acids (n-3 PUFAs) are docosahexaenoic acid and eicosapentaenoic acid in the form of fish oils and α linolenic acid from flaxseed oil. Epidemiological studies suggested the benefits of n-3 PUFA on cardiovascular health. Intervention studies confirmed that the consumption of n-3 PUFA provided benefits for primary and secondary prevention of cardiovascular disease. Evidence from cellular and molecular research studies indicates that the cardioprotective effects of n-3 PUFA result from a synergism between multiple, intricate mechanisms that involve antiinflammation, proresolving lipid mediators, modulation of cardiac ion channels, reduction of triglycerides, influence on membrane microdomains and downstream cell signaling pathways and antithrombotic and antiarrhythmic effects. n-3 PUFAs inhibit inflammatory signaling pathways (nuclear factor-κ B activity) and down-regulate fatty acid (FA) synthesis gene expression (sterol regulatory element binding protein-1c) and up-regulate gene expression involved in FA oxidation (peroxisome proliferator-activated receptor α). This review examines the various mechanisms by which n-3 PUFA exert beneficial effects against CVD.

Depleted folate pool and dysfunctional mitochondria associated with defective mitochondrial folate proteins sensitize Chinese ovary cell mutants to tert-butylhydroperoxide-induced oxidative stress and apoptosis

Yi-Ling Ye, Ya-Tsun Chan, Hsiu-Chuan Liu, Hsin-Te Lu, Rwei-Fen S. Huang — 2009-08-28

Abstract: The functional role of mitochondrial (mt) folate-associated proteins in mammalian cells is not clearly understood. We investigated the respiratory function and apoptosis phenotype of Chinese hamster ovary (CHO) mutant cells with defective mt serine hydroxymethyltransferase (SHMT) activities (glyA) or with defective mt folate transporter (glyB) in the absence/presence of oxidant challenge. The mechanisms underlying their aberrant phenotypes were explored. Compared with CHOK1 wild-type cells, both mutants carried dysfunctional mitochondria with reduced respiratory complex IV activity and depolarized mt membrane potential (P<.05). Elevated superoxide levels and accumulated mtDNA large deletions were observed in glyB in association with a depleted compartmental folate pool (P<.05). tert-Butylhydroperoxide (tBH) treatment at 50 μM for 72 h significantly depleted mt and cytosolic folate levels, impaired antioxidant defenses, and aggravated mt oxidative dysfunction in both mutants (P<.05), more severely in glyB. Only tBH-treated glyB cells displayed an elevated ratio of mt Bax/Bcl-2, activation of procaspases 9 and 3, and apoptosis promotion. The apoptotic phenotype of tBH-treated glyB could be partially corrected by folate supplementation (10–1000 μM), which enriched compartmental folate levels, restored antioxidant defenses, eliminated mt oxidative injuries, and normalized mt membrane function. Our data identify previously unrecognized roles of mt folate-associated proteins in the protection of mitochondria against oxidative insults. Defective mt folate transporter sensitized glyB cells to elevated oxidative stress and tBH-induced apoptosis, partly mediated by depleted compartmental folate and mt dysfunction. Defective mt SHMT sensitized glyA to respiratory dysfunction and tBH-induced oxidative injury without apoptosis promotion.

Vitamin C supplementation prevents testosterone-induced hyperplasia of rat prostate by down-regulating HIF-1α

2009-08-28

Abstract: Benign prostatic hyperplasia (BPH) is a disease that impairs the well-being of many aged men. To alleviate BPH symptoms or to find a cure for this disease, key molecules should be identified that control prostate cell proliferation. Recently, HIF-1α has attracted attention in this context, because it is highly expressed in hyperplasic prostates and prevents prostate cell death. Thus, given that vitamin C inhibits HIF-1α expression in several malignant tumors, we examined its therapeutic potential in BPH. HIF-1α was noticeably induced by testosterone in prostate cells, and this HIF-1α induction was abolished by vitamin C. Vascular endothelial growth factor (VEGF) promoter activity reporter assays and semi-quantitative RT-PCR revealed that vitamin C inhibited HIF-1-dependent VEGF expression. Furthermore, HIF-1α suppression by vitamin C was rescued by knocking down HIF-prolyl hydroxylase-2, suggesting that vitamin C destabilizes HIF-1α via prolyl hydroxylation. Moreover, vitamin C treatment abolished cell proliferation induced by testosterone treatment to the control level. These results suggest that vitamin C inhibits testosterone-induced HIF-1α expression and by so doing effectively prevents prostate hyperplasia. In male rats, testosterone treatment for 4 weeks induced prostate hyperplasia. Furthermore, HIF-1α and VEGF levels were significantly elevated in hyperplasic prostates. In vitamin C-treated rats, however, most prostate hyperplasia parameters and prostrate HIF-1α/VEGF levels were markedly reduced. Accordingly, our findings indicate that vitamin C could be further developed clinically for use as an anti-BPH agent.

Caffeic acid phenethyl ester is a potent inhibitor of HIF prolyl hydroxylase: structural analysis and pharmacological implication

2009-09-10

Abstract: Caffeic acid phenethyl ester (CAPE) is an active component of propolis from honeybee. We investigated a potential molecular mechanism underlying a CAPE-mediated protective effect against ischemia/reperfusion (I/R) injury and analyzed the structure contributing to the CAPE effect. CAPE induced hypoxia-inducible factor-1 (HIF-1) α protein, concomitantly transactivating the HIF-1 target genes vascular endothelial growth factor and heme oxygenase-1, which play a protective role in I/R injury. CAPE delayed the degradation of HIF-1α protein in cells, which occurred by inhibition of HIF prolyl hydroxylase (HPH), the key enzyme for von Hippel–Lindau-dependent HIF-1α degradation. CAPE inhibition of HPH and induction of HIF-1α protein were neutralized by an elevated dose of iron. The catechol moiety, a chelating group, is essential for HPH inhibition, while hydrogenation of the double bond (–CC–) in the Michael reaction acceptor markedly reduced potency. Removal of the phenethyl moiety of CAPE (substitution with the methyl moiety) severely deteriorated its inhibitory activity for HPH. Our data suggest that a beneficial effect of CAPE on I/R injury may be ascribed to the activation of HIF-1 pathway via inhibition of HPH and reveal that the chelating moiety of CAPE acted as a pharmacophore while the double bond and phenethyl moiety assisted in inhibiting HPH.

4-Hydroxynonenal, a lipid peroxidation product of dietary polyunsaturated fatty acids, has anticarcinogenic properties in colon carcinoma cell lines through the inhibition of telomerase activity

2009-09-04

Abstract: The effects of polyunsaturated fatty acids (PUFAs) obtained from the diet on colorectal cancer have been widely explored. However, controversial results have been obtained about the role played by the lipid peroxidation products of PUFAs, such as 4-hydroxy-nonenal (HNE), in the control of colon cancer growth. This aldehyde, indeed, showed both procarcinogenic and protective effects. In an attempt to verify the action of HNE, we studied the effects of a low dose of HNE (1 μM), similar to those “physiologically” found in normal cells and plasma, on telomerase activity, a key parameter of malignant transformation. Caco-2 cells were exposed to HNE and, paralleling cell growth inhibition, we observed the down-regulation of telomerase activity and hTERT expression. Similar effects have also been observed in HT-29 cells, in which HNE inhibited cell proliferation, telomerase activity and hTERT expression, suggesting that the inhibition of telomerase activity could be a general mechanism involved in the antiproliferative effect exerted by this aldehyde. Finally, we elucidated the mechanism of hTERT inhibition by HNE. A reduction of GSH content preceded the decrease of telomerase activity, but this only partially explained the telomerase activity inhibition. The major mechanism of HNE action seems to be the modulation of expression and activity of transcription factors belonging to the Myc/Mad/Max network.Since the presence of PUFAs in the diet exposes epithelial colon cells to HNE, this aldehyde could contribute to cell growth control through the inhibitory action on telomerase activity and hTERT expression, suggesting a protective effect on colon mucosa.

Antioxidant treatment protects diabetic rats from cardiac dysfunction by preserving contractile protein targets of oxidative stress

2009-12-02

Abstract: Backgound: Animal studies suggest that reactive oxygen species (ROS) play an important role in the development of diabetic cardiomyopathy.Hypothesis: Matrix metalloproteinase-2 (MMP-2) is activated by ROS and contributes to the acute loss of myocardial contractile function by targeting and cleaving susceptible proteins including troponin I (TnI) and α-actinin.Methods: Using the streptozotocin-induced diabetic rat model, we evaluated the effect of daily in vivo administration of sodium selenate (0.3 mg/kg; DMS group), or a pure omega-3 fish oil with antioxidant vitamin E (omega-3E; 50 mg/kg; DMFA group), which has antioxidant-like effects, for 4 weeks on heart function and on several biochemical parameters related to oxidant stress and MMP-2.Results: Although both treatments prevented the diabetes-induced depression in left ventricular developed pressure (LVDP) as well as the rates of changes in developed pressure (±dP/dt) (P<.001), the improvement in LVDP of the DMS group was greater compared to that of the DMFA group (P<.001). Moreover, these treatments reduced the diabetes-induced increase in myocardial oxidized protein sulfhydryl and nitrite concentrations (P<.001). Gelatin zymography and Western blot data indicated that the diabetes-induced changes in myocardial levels of MMP-2 and tissue inhibitor of matrix metalloproteinase-4 (TIMP-4) and the reduction in TnI and α-actinin protein levels were improved in both the DMS and DMFA groups (P<.001).Conclusions: These results suggest that diabetes-induced alterations in MMP-2 and TIMP-4 contribute to myocardial contractile dysfunction by targeting TnI and α-actinin and that sodium selenate or omega-3E could have therapeutic benefits in diabetic cardiomyopathy.

Lipoprotein metabolism mediates the association of MTP polymorphism with β-cell dysfunction in healthy subjects and in nondiabetic normolipidemic patients with nonalcoholic steatohepatitis

Giovanni Musso, Roberto Gambino, Maurizio Cassader — 2009-09-07

Abstract: Nonalcoholic steatohepatitis (NASH) predicts incident diabetes independently of insulin resistance, adiposity and metabolic syndrome through unclear mechanisms. Dietary fat consumption and lipoperoxidative stress predispose to diabetes in the general population and to liver injury in NASH. Microsomal triglyceride transfer protein (MTP) polymorphism modulates lipoprotein metabolism in the general population and liver disease in NASH; a functional MTP polymorphism recently predicted incident diabetes independently of insulin resistance in the general population. We simultaneously assessed the impact of MTP polymorphism, diet, adipokines and lipoprotein metabolism, on glucose homeostasis in NASH.MTP −493G/T polymorphism, dietary habits, adipokines and postprandial triglyceride-rich lipoproteins, high-density lipoprotein cholesterol (HDL-C) and oxidized low-density lipoprotein (oxLDL) responses to an oral fat load, were cross-sectionally correlated to oral glucose tolerance test- and frequently sampled intravenous glucose tolerance test-derived Minimal Model indexes of glucose homeostasis in 40 nondiabetic normolipidemic patients with NASH and 40 age-,sex- and body mass index-matched healthy controls.Despite comparable insulin resistance, fasting lipids, adipokines and dietary habits, MTP GG genotype had significantly more severe β-cell dysfunction; higher plasma Tg, FFA, intestinal and hepatic very low-density lipoprotein 1 subfractions and oxLDL responses and deeper HDL-C fall than GT/TT carriers in patients and controls.Postprandial HDL-C and oxLDL responses independently predicted β-cell dysfunction and mediated the effect of MTP polymorphism on β-cell function.In nondiabetic normolipidemic NASH, MTP −493G/T polymorphism modulates β-cell function, an effect mediated by postprandial HDL-C and oxLDL metabolism. The impact of this polymorphism on the risk of diabetes and the efficacy of lipid-lowering therapies in restoring β-cell function in NASH, even with normal fasting lipid values, warrant further investigation.

Daidzein and the daidzein metabolite, equol, enhance adipocyte differentiation and PPARγ transcriptional activity

2010-09-01

Abstract: Dietary soy isoflavones have been shown to favorably alter the metabolic phenotypes associated with Type 2 diabetes. However, the identification of direct targets and the underlying molecular mechanisms by which soy isoflaovones exert antidiabetic effects remain elusive. Since the insulin-sensitizing effects of thiazolidinediones, antidiabetic drugs, are mediated through activation of peroxisome proliferators-activated receptor gamma (PPARγ), we examined the effects of daidzein and the daidzein metabolite, equol, on adipocyte differentiation and PPARγ activation. In 3T3-L1 cells, daidzein enhanced adipocyte differentiation and PPARγ expression in a dose-dependent manner. Daidzein also dose-dependently increased insulin-stimulated glucose uptake and the relative abundance of insulin-responsive glucose transporter 4 (GLUT4) and insulin receptor substrate 1 (IRS-1) mRNA. In C3H10T1/2 cells, both daidzein and equol at 1 μmol/L and higher significantly increased adipocyte differentiation and insulin-stimulated glucose uptake. Furthermore, daidzein and equol up-regulated PPARγ-mediated transcriptional activity, and daidzein restored the PPARγ antagonist-induced inhibition of aP2 and GLUT4 mRNA levels. Our results indicate that daidzein enhances insulin-stimulated glucose uptake in adipocytes by increasing the expression of GLUT4 and IRS-1 via the activation of PPARγ. These data further support the recent findings that favorable effects of dietary soy isoflavones may be attributable to daidzein and its metabolite equol.

Trans-10, cis-12-conjugated linoleic acid alters hepatic gene expression in a polygenic obese line of mice displaying hepatic lipidosis

2009-10-05

Abstract: The trans-10, cis-12 isomer of conjugated linoleic acid (CLA) causes a rapid reduction of body and adipose mass in mice. In addition to changes in adipose tissue, numerous studies have reported alterations in hepatic lipid metabolism. Livers of CLA-fed mice gain mass, partly due to lipid accumulation; however, the precise molecular mechanisms are unknown. To elucidate these mechanisms, we examined fatty acid composition and gene expression profiles of livers from a polygenic obese line of mice fed 1% trans-10, cis-12-CLA for 14 days. Analysis of gene expression data led to the identification of 1393 genes differentially expressed in the liver of CLA-fed male mice at a nominal P value of .01, and 775 were considered significant using a false discovery rate (FDR) threshold of .05. While surprisingly few genes in lipid metabolism were impacted, pathway analysis found that protein kinase A (PKA) and cyclic adenosine monophosphate (cAMP) pathways signaling pathways were affected by CLA treatment and 98 of the 775 genes were found to be regulated by hepatocyte nuclear factor 4α, a transcription factor important in controlling liver metabolic status.

Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells

Takako Sakamoto, Hyogo Horiguchi, Etsuko Oguma, Fujio Kayama — 2009-10-05

Abstract: Phytoestrogens have attracted attention as being safer alternatives to hormone replacement therapy (HRT) and as chemopreventive reagents for breast cancer because dietary soy isoflavone intake has been correlated with reduction in risk. To identify safe and effective phytoestrogen candidates for HRT and breast cancer prevention, we investigated the effects of daidzein, genistein, coumestrol, resveratrol and glycitein on cell growth, cell cycle, cyclin D1 expression, apoptosis, Bcl-2/Bax expression ratio and p53-dependent or NF-κB-dependent transcriptional activity in MCF-7 breast cancer cells. Phytoestrogens, except for glycitein, significantly enhanced estrogen-response-element-dependent transcriptional activity up to a level similar to that of 17β-estradiol (E2). E2 increased cell growth significantly, coumestrol increased cell growth moderately, and resveratrol and glycitein reduced cell growth. Phytoestrogens, except for glycitein, stimulated the promotion of cells to G1/S transition in cell cycle analysis, similar to E2. This stimulation was accompanied by transient up-regulation of cyclin D1. While genistein, resveratrol and glycitein all increased apoptosis and reduced the Bcl-2/Bax ratio, resveratrol reduced this ratio more than either genistein or glycitein. Moreover, resveratrol significantly enhanced p53-dependent transcriptional activity, but slightly reduced NF-κB-dependent transcriptional activity. On knockdown analysis, genistein, resveratrol and glycitein all reduced the Bcl-2/Bax ratio in the presence of apoptosis-inducing stimuli, and estrogen receptor (ER) α silencing had no effect on these reductions. In contrast, in the absence of apoptosis-inducing stimuli, only resveratrol reduced the ratio, and ERα silencing abolished this reduction. Thus, resveratrol might be the most promising candidate for HRT and chemoprevention of breast cancer due to its estrogenic activity and high antitumor activity.

Potential immunoregulatory role of heme oxygenase-1 in human milk: a combined biochemical and molecular modeling approach

2009-11-02

Abstract: Human milk contains biological factors that are involved in a newborn's growth and immune system regulation. By integrating standard biochemical experimental protocols with computational methods, the present study investigates the presence of heme oxygenase-1 (HO-1), a cytoprotective enzyme, in human milk at different levels of maturation and in milk formulae. Furthermore, we evaluated cytokine and glutathione S-transferase (GSH) levels. Samples were collected from colostrum (on Day 1 after birth), from transition milk (on Postdelivery Days 7 and 14) and from mature milk (on Day 30 after delivery) in 14 healthy women. HO-1 protein, GSH and cytokines levels were measured using enzyme-linked immunosorbent assay and flow cytometry. HO-1 protein levels were significantly higher in colostrum (1.33 ng/ml; 5th centile 0.92; 95th centile 2.38) and in transition milk at 14 days (0.97 ng/ml; 5th centile 0.87; 95th centile 1.45) than in mature milk (0.9 ng/ml; 5th centile 0.8; 95th centile 1.38). Levels of HO-1 in milk formulae were similar to those in colostrum. No significant differences in GSH content were observed in mature milk, transition milk and colostrum, whereas significantly higher GSH levels were observed in milk formulae. No significant levels of cytokines, with the exception of interleukin-8, were found. Computational studies on the possible interactions between HO-1 and CD91 were carried out by a battery of softwares, namely, GRAMM (version 1.03), DALI, CLUSTALW (version 2.0), PatchDock and FireDock, mutually counterchecking and validating each other. The computational results, the strong convergence (to the same “solution”) of which finally leads to an “experimental-like” character, showed that HO-1 may bind to CD91, thus suggesting its major role as a new chaperokine in immune response regulation. These findings, which connect and integrate biochemical data and computational data interpretation, represent a synergistic and powerful means of conducting biological research.

Folic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese/diabetic mice

2009-11-02

Abstract: Folic acid supplementation provides beneficial effects on endothelial functions in patients with hyperhomocysteinemia. However, its effects on vascular functions under diabetic conditions are largely unknown. Therefore, the effect(s) of folic acid (5.7 and 71 μg/kg/day for 4 weeks) on aortic relaxation was investigated using obese/diabetic (+db/+db) mice and lean littermate (+db/+m) mice. Acetylcholine-induced relaxation in +db/+db mice was less than that observed in +db/+m mice. The reduced relaxation in +db/+db mice was restored by consumption of 71 μg/kg folic acid. Acetylcholine-induced relaxation (with and without folic acid treatment) was sensitive to NG-nitro-l-arginine methyl ester, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, geldanamycin and triciribine. In addition, acetylcholine-induced relaxation was attenuated by resistin. The plasma level of resistin in +db/+db mice was sevenfold higher than that measured in +db/+m mice, and the elevated plasma level of resistin in +db/+db mice was reduced by 25% after treatment with 71 μg/kg folic acid. Folic acid slightly increased the ratio of reduced glutathione to oxidized glutathione in +db/+db mice. Moreover, folic acid caused a reduction in PTEN (phosphatase and tensin homolog deleted on chromosome 10) expression, an increase in the phosphorylation of endothelial nitric oxide synthase (eNOSSer1177) and AktSer473, and an enhanced interaction of heat shock protein 90 (HSP90) with eNOS in both strains, with greater magnitude observed in +db/+db mice. In conclusion, folic acid consumption improved blunted acetylcholine-induced relaxation in +db/+db mice. The mechanism may be, at least partly, attributed to enhancement of PI3K/HSP90/eNOS/Akt cascade, reduction in plasma resistin level, down-regulation of PTEN and slight modification of oxidative state.

Evaluation of cardiovascular risk and oxidative stress parameters in hypercholesterolemic subjects on a standard healthy diet including low-fat milk enriched with plant sterols

2009-11-04

Abstract: A healthy diet and plant sterols (PS) are recommended for reducing low-density lipoprotein (LDL) cholesterol and, subsequently, the risk of premature cardiovascular disease. PS mediate a decrease in fat-soluble vitamin concentration, which can lead to a general impairment of antioxidative defenses and an increase in oxidative stress. Thus, we evaluated the effects of a healthy diet, including PS-enriched low-fat milk, on cardiovascular risk and oxidative stress parameters in hypercholesterolemic subjects.This was a randomized parallel trial employing 40 subjects and consisting of two 3-month intervention phases. After 3 months on a standard healthy diet, subjects were divided into two intervention groups: a diet group and a diet+PS group (2 g/day). Lipid profile, apolipoproteins, high-sensitivity C-reactive protein and oxidative stress parameters were analyzed. Diet significantly reduced total and LDL cholesterol (4.0% and 4.7%, respectively), produced an increase in the level of β-carotene (23%) and improved the antioxidant capacity of LDL cholesterol particles (4.6%). PS induced a significant decrease in total cholesterol (6.4%), LDL (9.9%) and the apolipoprotein B100/apolipoprotein A1 ratio (4.9%), but led to a decrease in cryptoxanthin level (29%) without any change being observed in the antioxidant capacity of LDL cholesterol particles, total antioxidant status or lipid peroxidation. After 3 months, we observed the positive effect of including a PS supplement in dietary measures, as the lipoprotein-mediated risk of cardiovascular disease was reduced. Despite a decrease in the concentration of cryptoxanthin, no evidence of a global impairment of antioxidative defenses or an enhancement of oxidative stress parameters was found.

Cloning, yeast expression, purification and biological activity of a truncated form of the soybean 7S globulin α′ subunit involved in Hep G2 cell cholesterol homeostasis

2009-12-02

Abstract: A truncated form of α′ chain (tα′), the soybean 7S globulin subunit previously demonstrated to be active in controlling the cholesterol and triglyceride homeostasis in in vitro and in vivo models, was cloned and expressed in the yeast Pichia pastoris. The recombinant polypeptide spanned 216 amino acid residues from the N-terminal side and included the N-terminal extension region of the soybean subunit. The tα′ polypeptide was purified by conventional biochemical techniques, and its potential to modulate the activity of low-density lipoprotein (LDL) receptor was evaluated in a human hepatoma cell line (Hep G2) by monitoring the uptake and degradation of labeled LDL. The LDL uptake (+192%) and degradation (+143%) by cells tested at the highest tα′ dose (8 μM) were similar to those found in cells incubated with 1 μM simvastatin, a potent inhibitor of cholesterol biosynthesis. The cell response to tα′ was found to be dose dependent. The use of a recombinant polypeptide ruled out the involvement of any other soybean component.These findings open new prospects in the studies aimed at identifying soybean regulatory (poly)peptide(s) and the mechanism involved in this biological response, as a gateway to their utilization for the management of human health.

Reduction in systemic and VLDL triacylglycerol concentration after a 3-month Mediterranean-style diet in high-cardiovascular-risk subjects

2009-12-07

Abstract: The first results of the PREDIMED (PREvencion con Dieta MEDiterranea) randomized trial, after 3-month intervention, showed that the Mediterranean Diet (MD), supplemented with either virgin olive oil (VOO) or nuts, reduced systolic blood pressure, serum cholesterol and triacylglycerol (TG) concentrations and increased high-density lipoprotein (HDL)-cholesterol when compared to a control (low-fat diet) group. Serum TG levels are an independent risk factor for coronary heart disease and are strongly determined by very low-density lipoprotein (VLDL) composition, which can be specifically modified by dietary lipid source. Within the context of the PREDIMED study, we assessed the VLDL composition in 50 participants after 3 months of intake of two MD, supplemented with VOO or nuts, compared with a low-fat diet. Total and low-density lipoprotein cholesterol concentrations were reduced in subjects on the MD+nuts, whereas HDL-cholesterol increased after consumption of the MD+VOO. Serum TG concentrations were significantly lowered in both intervention groups (either the MD+nuts or MD+VOO). However, only the MD+VOO reduced the VLDL-cholesterol and VLDL-TG content and the TG/apolipoprotein B ratio in VLDL, which was used to estimate particle size. Although VLDL-TG fatty acids were very slightly modified, VLDL-TG molecular species in VLDL after consumption of the MD+nuts were characterized by a higher presence of linoleic acid (18:2, n-6), whereas after the intake of MD+VOO, they were rich in oleic acid (18:1, n-9). Therefore, we conclude that the reduction in systemic TG concentrations observed after consumption of the MD may be explained by reduction of the lipid core of VLDL and a selective modification of the molecular species composition in the particle.

The Journal of Nutritional Biochemistry

Table of Contents

Mechanisms underlying the cardioprotective effects of omega-3 polyunsaturated fatty acids

Depleted folate pool and dysfunctional mitochondria associated with defective mitochondrial folate proteins sensitize Chinese ovary cell mutants to tert-butylhydroperoxide-induced oxidative stress and apoptosis

Vitamin C supplementation prevents testosterone-induced hyperplasia of rat prostate by down-regulating HIF-1α

Caffeic acid phenethyl ester is a potent inhibitor of HIF prolyl hydroxylase: structural analysis and pharmacological implication

4-Hydroxynonenal, a lipid peroxidation product of dietary polyunsaturated fatty acids, has anticarcinogenic properties in colon carcinoma cell lines through the inhibition of telomerase activity

Antioxidant treatment protects diabetic rats from cardiac dysfunction by preserving contractile protein targets of oxidative stress

Lipoprotein metabolism mediates the association of MTP polymorphism with β-cell dysfunction in healthy subjects and in nondiabetic normolipidemic patients with nonalcoholic steatohepatitis

Daidzein and the daidzein metabolite, equol, enhance adipocyte differentiation and PPARγ transcriptional activity

Trans-10, cis-12-conjugated linoleic acid alters hepatic gene expression in a polygenic obese line of mice displaying hepatic lipidosis

Effects of diverse dietary phytoestrogens on cell growth, cell cycle and apoptosis in estrogen-receptor-positive breast cancer cells

Potential immunoregulatory role of heme oxygenase-1 in human milk: a combined biochemical and molecular modeling approach

Folic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese/diabetic mice

Evaluation of cardiovascular risk and oxidative stress parameters in hypercholesterolemic subjects on a standard healthy diet including low-fat milk enriched with plant sterols

Cloning, yeast expression, purification and biological activity of a truncated form of the soybean 7S globulin α′ subunit involved in Hep G2 cell cholesterol homeostasis

Reduction in systemic and VLDL triacylglycerol concentration after a 3-month Mediterranean-style diet in high-cardiovascular-risk subjects