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Objective: Cholesterol levels have been reported to be lower in suicidal patients, and alterations in blood levels of polyunsaturated fatty acids have been found in people with depression. Given that [...]

Cranberry fruit has been reported to have high antioxidant effectiveness that is potentially linked to its richness in diversified polyphenolic content. The aim of the present study was to determine the role of cranberry polyphenolic fractions in oxidative stress (OxS), inflammation and mitochondrial functions using intestinal Caco-2/15 cells. The combination of HPLC and UltraPerformance LC®-tandem quadrupole (UPLC-TQD) techniques allowed us to characterize the profile of low, medium and high molecular mass polyphenolic compounds in cranberry extracts. The medium molecular mass fraction was enriched with flavonoids and procyanidin dimers whereas procyanidin oligomers (DP > 4) were the dominant class of polyphenols in the high molecular mass fraction. Pre-incubation of Caco-2/15 cells with these cranberry extracts prevented iron/ascorbate-mediated lipid peroxidation and counteracted lipopolysaccharide-mediated inflammation as evidenced by the decrease in pro-inflammatory cytokines (TNF-a and interleukin-6), cyclo-oxygenase-2 and prostaglandin E2. Cranberry polyphenols (CP) fractions limited both nuclear factor KB activation and Nrf2 down-regulation. Consistently, cranberry procyanidins alleviated OxS-dependent mitochondrial dysfunctions as shown by the rise in ATP production and the up-regulation of Bcl-2, as well as the decline of protein expression of cytochrome c and apoptotic-inducing factor. These mitochondrial effects were associated with a significant stimulation of peroxisome-proliferator-activated receptor y co-activator-1-a, a central inducing factor of mitochondrial biogenesis and transcriptional co-activator of numerous downstream mediators. Finally, cranberry procyanidins forestalled the effect of iron/ascorbate on the protein expression of mitochondrial transcription factors (mtTFA, mtTFB1, mtTFB2). Our findings provide evidence for the capacity of CP to reduce intestinal OxS and inflammation while improving mitochondrial dysfunction. [ABSTRACT FROM AUTHOR]

Alternative HPLC and solid-phase extraction column methods were developed to separate metabolites of enzymes involved in cholesterol metabolism in rabbit liver microsomes: hydroxyl-methylglutaryl-CoA reductase, cholesterol-7 α-hydroxylase and acyl-CoA:cholesterol acyltransferase. A comparison method of thin-layer chromatography and solid-phase extraction column were assayed to separate substrate and metabolite of hydroxy-methylglutaryl-CoA reductase, whereas for cholesterol-7 α-hydroxylase and acyl-CoA:cholesterol acyltransferase, this comparison was done between thin layer chromatography and HPLC. The results obtained by the new analytical chromatographic methods are not significantly different than those observed in literature. Moreover a larger percentage recovery was obtained for analysed metabolites. Our results demonstrate the reliability of these alternative chromatographic techniques and showed that they are valuable tools to precisely and rapidly measure the activity of those enzymes. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Fetal development requires an important entry of essential free fatty acids (EFFA) and essential amino acids (EAA) into the fetal circulation. We have reported that a 0.2% enriched-cholesterol diet (ECD) during rabbit gestation significantly reduces fetus weight compared to control diet. It is known that dietary linoleic acid deficiency, an EFFA, during the fetal development induces an important impair to the somatic development. Moreover, intrauterine growth retardation induced a reduction of the flux of leucine, an EAA, from maternal to fetal circulation. Therefore, we hypothesized that the administration of an ECD induces modifications of placental lipid composition concomitant alterations of the transfer of linoleic acid and leucine in fetal circulation. Quantification of placental lipids revealed that in the ECD group a reduction of total-cholesterol (TC) and free-cholesterol (FC) is observed, however an increased in FFA and phospholipids is noticed when compared to the control group. In placenta from the ECD group, the FC/ TC ratio is significantly reduced compared to the control group. In the ECD group, the liver shows an increase of TC, FC and FFA compared to the control group. However, the quantity of triacylglycerol present in the liver from the ECD is significantly reduced compared to the control group. To evaluate the placental transfer of some essential nutrients, intravenous injection of [1-14C]-linoleic acid or L-[4, 5-3H]-leucine to term rabbit (control and ECD group) were done. Two hours later, rabbits were euthanized and we collected placenta, livers and blood from dams and offspring. The concentrations of both radiolabeled molecules (linoleic acid and its esterified form or leucine) were higher in the plasma of ECD offspring than those found in offspring from control diet. Despite such alteration of placental lipid composition, linoleic acid and leucine transfer by the placenta was not compromised but rather increased. [Copyright &y& Elsevier]

The role of intestinal fatty acid binding protein (I-FABP) in lipid metabolism remains elusive. To address this issue, normal human intestinal epithelial cells (HIEC-6) were transfected with cDNA to overexpress I-FABP and compared with cells treated with empty pQCXIP vector. I-FABP overexpression stimulated mitochondrial [U-14C]oleate oxidation to CO2 and acid-soluble metabolites via mechanisms including the upregulation of protein expression and the activity of carnitine palmitoyltransferase 1, a critical enzyme controlling the entry of fatty acid (FA) into mitochondria, and increased activity of 3-hydroxyacyl-CoA dehydrogenase, a mitochondrial beta-oxidation enzyme. On the other hand, the gene and protein expression of the key enzymes FA synthase and acetyl-coenzyme A carboxylase 2 was decreased, suggesting diminished lipogenesis. Furthermore, I-FABP overexpression caused a decline in [14C]free cholesterol (CHOL) incorporation. Accordingly, a significant lessening was observed in the gene expression of Niemann Pick C1-Like 1, a mediator of CHOL uptake, along with an increase in the transcripts and protein content of ABCA1 and ABCG5/ABCG8, acting as CHOL efflux pumps. Furthermore, I-FABP overexpression resulted in increased levels of mRNA, protein mass, and activity of HMG-CoA reductase, the rate-limiting step in CHOL synthesis. Scrutiny of the nuclear receptors revealed augmented peroxisome proliferator-activated receptor alpha,gamma and reduced liver X receptor-alpha in HIEC-6 overexpressing I-FABP. Finally, I-FABP overexpression did not influence acyl-coenzyme A oxidase 1, which catalyzes the first rate-limiting step in peroxisomal FA beta-oxidation. Overall, our data suggest that I-FABP may influence mitochondrial FA oxidation and CHOL transport by regulating gene expression and interaction with nuclear receptors.