Lutein, zeaxanthin and mammalian development: Metabolism, functions and implications for health.

It is now widely accepted that nutrition during critical periods in early development, both pre- and postnatal, may have lifetime consequences in determining health or onset of major diseases in the adult life. Dietary carotenoids have shown beneficial health effects throughout the life cycle due to their potential antioxidant properties, their ability to serves as precursors of vitamin A and to the emerging signaling functions of their metabolites. The non-provitamin A carotenoids lutein and zeaxanthin are emerging as important modulators of infant and child visual and cognitive development, as well as critical effectors in the prevention and treatment of morbidity associated with premature births. This review provides a general overview of lutein and zeaxanthin metabolism in mammalian tissues and highlights the major advancements and remaining gaps in knowledge in regards to their metabolism and health effects during pre- and early post-natal development. Furthering our knowledge in this area of research will impact dietary recommendation and supplementation strategies aimed at sustaining proper fetal and infant growth.

Soy isoflavones in nutritionally relevant amounts have varied nutrigenomic effects on adipose tissue.

Soy consumption has been suggested to afford protection from cardiovascular disease (CVD). Indeed, accumulated albeit controversial evidence suggests that daily consumption of ≥25 g of soy protein with its associated phytochemicals intact can improve lipid profiles in hypercholesterolemic humans. However, the belief that soy foods and supplements positively impact human health has become increasingly controversial among the general public because of the reported estrogenic activities of soy isoflavones. In this study, we investigated the nutrigenomic actions of soy isoflavones (in nutritionally-relevant amounts) with a specific focus on the adipose tissue, due to its pivotal role in cardiometabolism. Young C57BL/6 mice were maintained for eight weeks under two different diet regimes: (1) purified control diet; or (2) purified control diet supplemented with 0.45 g% soybean dry purified extract (a genistein/daidzein mix). Soy isoflavones increased plasma total cholesterol concentrations and decreased triglyceride ones. Circulating leptin levels was also increased by soy consumption. Differentially expressed genes in adipose tissue were classified according to their role(s) in cellular or metabolic pathways. Our data show that soy isoflavones, administered in nutritionally-relevant amounts, have diverse nutrigenomic effects on adipose tissue. Taking into account the moderate average exposure to such molecules, their impact on cardiovascular health needs to be further investigated to resolve the issue of whether soy consumption does indeed increase or decrease cardiovascular risk.

Docosahexaenoic acid modulates the enterocyte Caco-2 cell expression of microRNAs involved in lipid metabolism.

Consumption of the long-chain ω-3 (n-3) polyunsaturated fatty acid docosahexaenoic acid (DHA) is associated with a reduced risk of cardiovascular disease and greater chemoprevention. However, the mechanisms underlying the biologic effects of DHA remain unknown. It is well known that microRNAs (miRNAs) are versatile regulators of gene expression. Therefore, we aimed to determine if the beneficial effects of DHA may be modulated in part through miRNAs. Loss of dicer 1 ribonuclease type III (DICER) in enterocyte Caco-2 cells supplemented with DHA suggested that several lipid metabolism genes are modulated by miRNAs. Analysis of miRNAs predicted to target these genes revealed several miRNA candidates that are differentially modulated by fatty acids. Among the miRNAs modulated by DHA were miR-192 and miR-30c. Overexpression of either miR-192 or miR-30c in enterocyte and hepatocyte cells suggested an effect on the expression of genes related to lipid metabolism, some of which were confirmed by endogenous inhibition of these miRNAs. Our results show in enterocytes that DHA exerts its biologic effect in part by regulating genes involved in lipid metabolism and cancer. Moreover, this response is mediated through miRNA activity. We validate novel targets of miR-30c and miR-192 related to lipid metabolism and cancer including nuclear receptor corepressor 2, isocitrate dehydrogenase 1, DICER, caveolin 1, ATP-binding cassette subfamily G (white) member 4, retinoic acid receptor ß, and others. We also present evidence that in enterocytes DHA modulates the expression of regulatory factor X6 through these miRNAs. Alteration of miRNA levels by dietary components in support of their pharmacologic modulation might be valuable in adjunct therapy for dyslipidemia and other related diseases.

Hydroxytyrosol is not genotoxic in vitro.

Hydroxytyrosol (HT) is an olive-derived phenol endowed with several biological activities, some of which demonstrated in humans. Indeed, the European Food Safety Authority (EFSA) allows the health claim that HT (≥5mg/d) "protects LDL particles from oxidative damage". In terms of safety, HT has been investigated as the predominant part of raw olive mill waste water extracts that have been granted the Generally Recognized as Safe (GRAS) status. Also, a long-term toxicological study of HT proposed a NOAEL of 500mg/kg/d. As several HT-containing supplements and functional foods are entering the market, we sought to investigate the genotoxic and mutagenic potential of HT, using well-established in vitro models, i.e. the chromosomal aberration assay and the Ames test (by using the Salmonella typhimurium TA 100, TA98, TA1535, and TA1537 strains and Escherichia coli WP2(pKM101)), with and without S9-induced metabolic activation). Even though we cannot rule out that prolonged exposure to HT and its metabolites might have untoward effects, the results of this study indicate that HT is non-genotoxic and non-mutagenic at concentrations that far exceed those attainable after intake.

Effect of TiO2 and Al2O3 Addition on the Performance of Chitosan/Phosphotungstic Composite Membranes for Direct Methanol Fuel Cells.

Composite chitosan/phosphotungstic acid (CS/PTA) with the addition of TiO2 and Al2O3 particles were synthesized to be used as proton exchange membranes in direct methanol fuel cells (DMFCs). The influence of fillers was assessed through X-ray diffraction, scanning electron microscopy, thermogravimetric analysis, liquid uptake, ion exchange capacity and methanol permeability measurements. The addition of TiO2 particles into proton exchange membranes led to an increase in crystallinity and a decrease in liquid uptake and methanol permeability with respect to pristine CS/PTA membranes, whilst the effect of the introduction of Al2O3 particles on the characteristics of membranes is almost the opposite. Membranes were successfully tested as proton conductors in a single module DMFC of 1 cm2 as active area, operating at 50 °C fed with 2 M methanol aqueous solution at the anode and oxygen at the cathode. Highest performance was reached by using a membrane with TiO2 (5 wt.%) particles, i.e., a power density of 40 mW cm-2, almost doubling the performance reached by using pristine CS/PTA membrane (i.e., 24 mW cm-2).

Characterization of lipoproteins in human placenta and fetal circulation as well as gestational changes in lipoprotein assembly and secretion in human and mouse placentas.

In the maternal circulation, apoB-containing low-density lipoproteins (LDL) and apoA1-containing high-density lipoproteins (HDL) transport lipids. The production of lipoproteins in the placenta has been suggested, but the directionality of release has not been resolved. We compared apolipoprotein concentrations and size-exclusion chromatography elution profiles of lipoproteins in maternal/fetal circulations, and in umbilical arteries/veins; identified placental lipoprotein-producing cells; and studied temporal induction of lipoprotein-synthesizing machinery during pregnancy. We observed that maternal and fetal lipoproteins are different with respect to concentrations and elution profiles. Surprisingly, concentrations and elution profiles of lipoproteins in umbilical arteries and veins were similar indicating their homeostatic control. Human placental cultures synthesized apoB100-containing LDL-sized and apoA1-containing HDL-sized particles. Immunolocalization techniques revealed that ApoA1 was present mainly in syncytiotrophoblasts. MTP, a critical protein for lipoprotein assembly, was in these trophoblasts. ApoB was in the placental stroma indicating that trophoblasts secrete apoB-containing lipoproteins into the stroma. ApoB and MTP expressions increased in placentas from the 2nd trimester to term, whereas apoA1 expression was unchanged. Thus, our studies provide new information regarding the timing of lipoprotein gene induction during gestation, the cells involved in lipoprotein assembly and the gel filtration profiles of human placental lipoproteins. Next, we observed that mouse placenta produces MTP, apoB100, apoB48 and apoA1. The expression of genes gradually increased and peaked in late gestation. This information may be useful in identifying transcription factors regulating the induction of these genes in gestation and the importance of placental lipoprotein assembly in fetal development.

MRI radiomics: A machine learning approach for the risk stratification of endometrial cancer patients.

PURPOSE: To investigate radiomics and machine learning (ML) as possible tools to enhance MRI-based risk stratification in patients with endometrial cancer (EC). METHOD: From two institutions, 133 patients (Institution1 = 104 and Institution2 = 29) with EC and pre-operative MRI were retrospectively enrolled and divided in two a low-risk and a high-risk group according to EC stage and grade. T2-weighted (T2w) images were three-dimensionally annotated to obtain volumes of interest of the entire tumor. A PyRadiomics based and previously validated pipeline was used to extract radiomics features and perform feature selection. In particular, feature stability, variance and pairwise correlation were analyzed. Then, the least absolute shrinkage and selection operator technique and recursive feature elimination were used to obtain the final feature set. The performance of a Support Vector Machine (SVM) algorithm was assessed on the dataset from Institution 1 via 2-fold cross-validation. Then, the model was trained on the entire Institution 1 dataset and tested on the external test set from Institution 2. RESULTS: In total, 1197 radiomics features were extracted. After the exclusion of unstable, low variance and intercorrelated features least absolute shrinkage and selection operator and recursive feature elimination identified 4 features that were used to build the predictive ML model. It obtained an accuracy of 0.71 and 0.72 in the train and test sets respectively. CONCLUSIONS: Whole-lesion T2w-derived radiomics showed encouraging results and good generalizability for the identification of low-risk EC patients.

Physiological response to lipid peroxidation in ischemia and reperfusion during carotid endarterectomy.

BACKGROUND: In this study we aimed to assess lipid peroxidation during carotid endarterectomy by the formation of PUFA hydroperoxides (PUFAHP) and isoprostanes (IP) and concomitant peroxisomal beta-oxidation as a physiological mechanism to limit their concentration. Two markers of peroxisomal beta oxidation have been evaluated, formation of 2,3 dinor from IP and conjugated esadecadienoic acid (CD 16:2) from peroxisomal beta-oxidation of conjugated linoleic acid (CLA), an unusual fatty acid present in small concentration in our diet and preferentially beta-oxidised in peroxisomes.The study was conducted on 30 patients undergoing carotid endarterectomy. Blood samplings were performed before, during endarterectomy in the "ischemic phase", and 30 seconds, 30 minutes and 2 hours after reperfusion. RESULTS: The results showed that PUFAHP increased significantly after 30 min of reperfusion in patients with controlateral stenosis > 50%, and steeply decreased after 2 hour of reperfusion. Interestingly, IP increased in a similar fashion of PUFAHP but never significantly. Both ratios CD16:2/CLA and DIN/IP also increased significantly after 30 min of reperfusion to decrease thereafter. CONCLUSIONS: Our data show that lipid peroxidation takes place only in patients with high controlateral stenosis and within 2 hours occurs a physiological response aimed to decrease IP and PUFAHP by increasing their catabolism in peroxisomes.

Interplay between ß-carotene and lipoprotein metabolism at the maternal-fetal barrier.

Vitamin A is an essential nutrient, critical for proper embryonic development in mammals. Both embryonic vitamin A-deficiency or -excess lead to congenital malformations or lethality in mammals, including humans. This is due to the defective transcriptional action of retinoic acid, the active form of vitamin A, that regulates in a spatial- and temporal-dependent manner the expression of genes essential for organogenesis. Thus, an adequate supply of vitamin A from the maternal circulation is vital for normal mammalian fetal development. Provitamin A carotenoids circulate in the maternal bloodstream and are available to the embryo. Of all the dietary carotenoids, ß-carotene is the main vitamin A precursor, contributing at least 30% of the vitamin A intake in the industrialized countries and often constituting the sole source of retinoids (vitamin A and its derivatives) in the developing world. In humans, up to 40% of the absorbed dietary ß-carotene is incorporated in its intact form in chylomicrons for distribution to other organs within the body, including the developing tissues. Here, it can serve as a source of vitamin A upon conversion into apocarotenoids by its cleavage enzymes. Given that ß-carotene is carried in the bloodstream by lipoproteins, and that the placenta acquires, assembles and secretes lipoproteins, it is becoming evident that the maternal-fetal transfer of ß-carotene relies on lipoprotein metabolism. Here, we will explore the current knowledge about this important biological process, the cross-talk between carotenoid and lipid metabolism in the context of the maternal-fetal transfer of this provitamin A precursor, and the mechanisms whereby ß-carotene is metabolized by the developing tissues. This article is part of a Special Issue entitled Carotenoids recent advances in cell and molecular biology edited by Johannes von Lintig and Loredana Quadro.

Endocannabinoids may mediate the ability of (n-3) fatty acids to reduce ectopic fat and inflammatory mediators in obese Zucker rats.

Dietary (n-3) long-chain PUFA [(n-3) LCPUFA] ameliorate several metabolic risk factors for cardiovascular diseases, although the mechanisms of these beneficial effects are not fully understood. In this study, we compared the effects of dietary (n-3) LCPUFA, in the form of either fish oil (FO) or krill oil (KO) balanced for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) content, with a control (C) diet containing no EPA and DHA and similar contents of oleic, linoleic, and alpha-linolenic acids, on ectopic fat and inflammation in Zucker rats, a model of obesity and related metabolic dysfunction. Diets were fed for 4 wk. Given the emerging evidence for an association between elevated endocannabinoid concentrations and metabolic syndrome, we also measured tissue endocannabinoid concentrations. In (n-3) LCPUFA-supplemented rats, liver triglycerides and the peritoneal macrophage response to an inflammatory stimulus were significantly lower than in rats fed the control diet, and heart triglycerides were lower, but only in KO-fed rats. These effects were associated with a lower concentration of the endocannabinoids, anandamide and 2-arachidonoylglycerol, in the visceral adipose tissue and of anandamide in the liver and heart, which, in turn, was associated with lower levels of arachidonic acid in membrane phospholipids, but not with higher activity of endocannabinoid-degrading enzymes. Our data suggest that the beneficial effects of a diet enriched with (n-3) LCPUFA are the result of changes in membrane fatty acid composition. The reduction of substrates for inflammatory molecules and endocannabinoids may account for the dampened inflammatory response and the physiological reequilibration of body fat deposition in obese rats.

Effects of an oral contraceptive containing drospirenone on bone turnover and bone mineral density.

OBJECTIVE: To compare the effects of a new 21-day combined oral contraceptive containing 30 microg ethinyl/estradiol plus 3 mg drospirenone with a 21-day preparation containing 30 microg ethinyl/estradiol plus 75 microg gestodene on bone turnover and bone mineral density in young fertile women. METHODS: A randomized, controlled trial was conducted with healthy fertile women treated with 30 microg ethinyl/estradiol plus 3 mg drospirenone (group A; n = 24), 30 microg ethinyl/estradiol plus 75 microg gestodene (group B; n = 24) and healthy controls (group C, n = 23). At 3, 6, 9, and 12 months of the study, serum and urinary calcium, osteocalcin, urinary pyridinoline, and deoxypyridinoline were measured. At baseline and after 12 months, lumbar bone mineral density was determined by dual-energy X-ray absorptiometry. RESULTS: In groups A and B, urinary pyridinoline and deoxypyridinoline at 6, 9, and 12 months were significantly reduced in comparison with basal values and group C (P < .05). Pyridinoline and deoxypyridinoline levels were lower in group A than in group B throughout the study, but not significantly. In group A serum calcium levels were significantly increased after 6 months. At 12 months, no significant difference was detected in lumbar bone mineral density values among the 3 groups and in comparison with basal values. CONCLUSION: Both combined oral contraceptives exert a similar positive influence on bone turnover and bone-sparing effect in young postadolescent women.

[Biomonitoring of nurses occupationally exposed to antineoplastic drugs: the IMEPA Project]. / Identificazione di marcatori specifici di esposizione professionale a farmaci antiblastici usati in polichemioterapia: Progetto IMEPA.

OBJECTIVE: To develop a multiple-endpoint monitoring system in order to assess and minimize long term risks in hospital nurses exposed to antiblastic drugs. DESIGN: Molecular epidemiology study. SETTING: S. Orsola-Malpighi Hospital in Bologna, Italy: nurses exposed to antiblastic drugs. PARTICIPANTS: 50 exposed subjects (8 males and 42 females) and 50 unexposed individuals (8 males and 42 females) matched for age and smoking habits. MAIN OUTCOME MEASURES: Urinary markers of exposure, Heat Shock Proteins (HSPs) 27, 70, 90, 110, immunologic biomarkers in peripheral blood lymphocytes: apoptosis, cell-cycle analysis G1-S-G, typization of Natural Killer cells (NK) and receptors micronuclei; frequency in peripheral blood lymphocytes and in exfoliated buccal mucosa cells; activation ofspecific oncogenes (bax, bcl2). RESULTS: 19/50 subjects showed urinary antiblastic drug levels (3 subjects MTX, 11 subjects CP, 5 subjects MTX and CP). No statistically significant differences were observed in all the considered biomarkers between the exposed and control groups. CONCLUSION: This biomonitoring study doesn't evidence any early significant effect associated to the exposure to antiblastic drugs.

3-O-Hydroxytyrosol glucuronide and 4-O-hydroxytyrosol glucuronide reduce endoplasmic reticulum stress in vitro.

Endoplasmic reticulum (ER) stress is important for atherosclerosis development and is mediated by the unfolded protein response (UPR). In this work, we synthesized two among the most physiologically-prominent hydroxytyrosol HT hepatic metabolites, i.e. 3-O-HT glucuronide and 4-O-HT glucuronide and we tested their activities on ER stress (in human hepatocarcinoma HepG2 cells), to gain further insight into the cardiopreventive properties of HT, extra virgin olive oil, and the Mediterranean diet. We report that 3-O-HT glucuronide and 4-O-HT glucuronide inhibit tunicamycin-induced ER stress. As compared with the effects of the parent molecule, 3-O-HT glucuronide and 4-O-HT glucuronide at 10 µM and 25 µM alone induced a milder change in mRNA expression levels of both CCAAT-enhancer-binding protein homologous protein (CHOP) and glucose regulated protein GRP78 immunoglobulin heavy chain binding protein (BiP). In conclusion, we add further evidence to the hypothesis that the HT intake might be atheroprotective and reiterate the usefulness to preferably use high-quality, high-(poly)phenol extra virgin olive oil as a prominent condiment.

Isomer-specific effects of conjugated linoleic acid on HDL functionality associated with reverse cholesterol transport.

High-density lipoproteins (HDLs) are atheroprotective because of their role in reverse cholesterol transport. The intestine is involved in this process because it synthesizes HDL, removes cholesterol from plasma and excretes it into the lumen. We investigated the role of selected dietary fatty acids on intestinal cholesterol uptake and HDL functionality. Caco-2 monolayers grown on Transwells were supplemented with either palmitic, palmitoleic, oleic, linoleic, docosahexaenoic, eicosapentaenoic, arachidonic or conjugated linoleic acids (CLAs): c9,t11-CLA; t9,t11-CLA; c10,t12-CLA. Cells synthesized HDL in the basolateral compartment for 24 h in the absence or presence of an antibody to SR-BI (aSR-BI), which inhibits its interaction with HDL. Free cholesterol (FC) accumulated to a greater extent in the presence than in the absence of aSR-BI, indicating net uptake of FC by SR-BI. Uptake's efficiency was significantly decreased when cells were treated with c9,t11-CLA relative to the other fatty acids. These differences were associated with lower HDL functionality, since neither SR-BI protein expression nor expression and alternative splicing of other genes involved lipid metabolism were affected. Only INSIG2 expression was decreased, with no increase of its target genes. Increasing pre-ß-HDL synthesis, by inducing ABCA1 and adding APOA1, resulted in reduced uptake of FC by SR-BI after c9,t11-CLA treatment, indicating reduced functionality of pre-ß-HDL. Conversely, treatment with c9,t11-CLA resulted in a greater uptake of FC and esterified cholesterol from mature HDL. Therefore, Caco-2 monolayers administered c9,t11-CLA produced a nonfunctional pre-ß-HDL but took up cholesterol more efficiently via SR-BI from mature HDL.

Effects of bilateral ovariectomy and postoperative hormonal replacement therapy with 17beta-estradiol or raloxifene on serum leptin levels.

OBJECTIVE: To verify the effects of hypoestrogenism and replacement therapy on body mass index (BMI) and leptin in ovariectomized women. DESIGN: We conducted a longitudinal study on 56 women undergoing abdominal bilateral ovariectomy divided into three groups: 19 untreated controls, 18 scheduled to receive 17beta-estradiol, and 19 on raloxifene starting 15 days after surgery. Height, weight, and BMI were recorded on the day of surgery, 5 and 15 days later, and then after 6 months. Leptin and estradiol concentrations were determined by radioimmunoassay on the day of surgery, days 1, 5, and 15, and 6 months after. RESULTS: Leptin levels rose significantly on the day after surgery [median (range): 18.2 (9.8-25.0), 12.5 (9.1-20.9), and 20.5 (12.9-24.5); P< 0.01 v basal] and returned to values similar to baseline on day 5 in all groups. Six months later, controls showed significantly higher leptin levels in comparison with both treated women and basal values [median (range): 19.7 (10.4-22.8), 11.0 (7.6-16.9), and 13.5 (9.1-14.8) ng/ml; P< 0.01). Estradiol levels decreased in all groups, reaching statistical significance 5 days after surgery ( P< 0.01 v basal). A significant rise was observed 6 months after surgery in women treated with estrogens ( P< 0.01). Six months after surgery, BMI increased in untreated controls in comparison with treated women and baseline, although not significantly. CONCLUSIONS: The absence of modifications in leptin on days 5 and 15 after ovariectomy suggests that, in humans, estrogens may not exert an important effect on leptin secretion. After 6 months, replacement therapy maintained leptin levels and BMI was unmodified, whereas untreated controls showed a significant increase in leptin and a trend toward higher BMI, suggesting that replacement therapy may prevent changes in fat distribution and in leptin levels.

Long-chain omega 3 fatty acids: molecular bases of potential antioxidant actions.

Several lines of investigation are being developed to assess the impact of polyunsaturated fatty acids, namely those of the omega 3 series, intake on oxidative stress. Keeping in mind that there might be a dose-response relation, in vivo and in vitro data strongly suggest that omega 3 fatty acids might act as anti- rather than pro-oxidant in several cells such as vascular cells, hence diminishing inflammation, oxidative stress, and, in turn, the risk of atherosclerosis and degenerative disorders such as cardiovascular disease.

Hydroxytyrosol attenuates tunicamycin-induced endoplasmic reticulum stress in human hepatocarcinoma cells.

SCOPE: Hydroxytyrosol (HT) is a phenolic compound peculiarly abundant in olives and it is being recognized as a protector of LDL from oxidation. In addition to lipid oxidation, one emerging risk factor for cardiovascular disease is ER stress. We tested the effect of HT on the modulation of ER stress in HepG2 cells. METHODS AND RESULTS: HepG2 cells were treated with 1 µM and 5 µM of HT and 100 µM lipoic acid (LA) and glutathione-ethyl ester (GSH), for 24 h. Induction of the unfolded protein response (UPR) was initiated by treatment with 2 µg/mL tunicamycin for 4 h. Real time RT-PCR analyses followed by Western blot and ELISA of different ER stress markers revealed that the protective activities of HT were superior to those of two known thiolic antioxidants, i.e., LA and GSH. CONCLUSION: Mounting evidence indicates the ER as an important target of dietary or pharmacological intervention. In this paper, we report the modulatory activities of physiological concentrations of HT toward ER stress and we shed some light on pathways alternative to the well-known antioxidant mechanisms, through which olive oil phenolics modulate cell signaling and could impact cardiovascular health and degenerative diseases.

Green tea, cocoa, and red wine polyphenols moderately modulate intestinal inflammation and do not increase high-density lipoprotein (HDL) production.

Although polyphenols are often merely perceived as antioxidants, their biological activities are manifold and include anti-inflammatory actions. A new area of research on polyphenols and health concerns their putative role in cholesterol metabolism, in particular, their high-density lipoprotein-cholesterol (HDL-c)-raising potential. Indeed, some human studies showed that administration of polyphenol-rich foods such as cocoa, green tea, and extra virgin olive oil modulate and increase HDL-c concentrations. This study assessed the effects of polyphenols on intestinal inflammation, using the physiologically relevant Caco-2 Transwell model and using lipopolysaccharide (LPS) to trigger inflammation. This study also investigated the mechanisms of actions behind the proposed HDL-c-increasing effects of polyphenols. The data suggest that polyphenols (at least those from red wine, cocoa, and green tea) administered at a dietary dose moderately modulate intestinal inflammation but do not increase cholesterol secretion by intestinal cells or enhance HDL functionality. Nutraceuticals and supplements provide pharmanutritional doses that might, conversely, produce beneficial effects.

Metabolic interactions between vitamin A and conjugated linoleic acid.

Lipid-soluble molecules share several aspects of their physiology due to their common adaptations to a hydrophilic environment, and may interact to regulate their action in a tissue-specific manner. Dietary conjugated linoleic acid (CLA) is a fatty acid with a conjugated diene structure that is found in low concentrations in ruminant products and available as a nutritional supplement. CLA has been shown to increase tissue levels of retinol (vitamin A alcohol) and its sole specific circulating carrier protein retinol-binding protein (RBP or RBP4). However, the precise mechanism of this action has not been elucidated yet. Here, we provide a summary of the current knowledge in this specific area of research and speculate that retinol and CLA may compete for catabolic pathways modulated by the activity of PPAR-α and RXR heterodimer. We also present preliminary data that may position PPAR-α at the crossroads between the metabolism of lipids and vitamin A.

Molecular targets of omega 3 and conjugated linoleic Fatty acids - "micromanaging" cellular response.

Essential fatty acids cannot be synthesized de novo by mammals and need to be ingested either with the diet or through the use of supplements/functional foods to ameliorate cardiovascular prognosis. This review focus on the molecular targets of omega 3 fatty acids and conjugated linoleic acid, as paradigmatic molecules that can be exploited both as nutrients and as pharmacological agents, especially as related to cardioprotection. In addition, we indicate novel molecular targets, namely microRNAs that might contribute to the observed biological activities of such essential fatty acids.