Fatty acid uptake by the placenta is thought to be a carrier-mediated process, however the mechanism by which long chain polyunsaturated fatty acids (LCPUFA) are preferentially accumulated from the maternal circulation to the fetal tissues is still unclear. To examine the role of the placenta in this process, binding of four different radiolabelled fatty acids (-14C-oleate, -14C-linoleate, [14C]a-linolenate and [14C]arachidonate) to human placental membranes was studied. Binding of fatty acid was found to be time- and temperature dependent. At equilibrium, the total binding of oleate was highest (5.1 +/- 0.1 nmoles/mg protein) followed by linoleate (2.8 +/- 0.31 nmoles/mg protein) and arachidonate (2.06 +/- 0.4 nmoles/mg protein) and alpha-linolenate binding was lowest (0.5 +/- 0.1 nmoles/mg protein). However, oleate had the lowest specific binding (37% of the total binding) whereas arachidonate had the highest specific binding (approximately 86% of the total binding) followed by linoleate and a-linolenate (62%, and 69% of the total binding, respectively). Binding of each [14C] fatty acid was also assessed in the presence of 20-fold excess of other unlabelled ligands. Binding sites seem to have preference for the binding of [14C] fatty acids in the following order: arachidonic acid >>> linoleic acid >> a-linolenic acid >>>>> oleic acid, whereas BSP and a-tocopherol did not show any competition with any of the [14C] fatty acids. These data suggest that the fatty acid binding sites in placental membranes are specific for the fatty acids but that they have heterogeneous affinities. Trans fatty acids (elaidic and linoelaidic acids) also competed very strongly for the [14C] fatty acid binding. Polyclonal antiserum raised against placental FABPpm inhibited binding of these [14C] fatty acids but with variable degrees of inhibition; EFA/LCPUFA binding was much more than that of oleate. Our data suggest that EFA/LCPUFA bound to albumin are preferentially transported by human placental membranes and that the placental FABPpm may be involved in the sequestration of EFA/LCPUFA by the placenta.

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Among all fruits tested in vitro for their anti-platelet property, tomato had the highest activity followed by grapefruit, melon, and strawberry, whereas pear and apple had little or no activity. Tomato extract (20-50 microl of 100% juice) inhibited both ADP- and collagen-induced aggregation by up to 70% but could not inhibit arachidonic acid-induced platelet aggregation and concomitant thromboxane synthesis under similar experimental conditions. The anti-platelet components (MW <1000 Da) in tomatoes are water soluble, heat stable and are concentrated in the yellow fluid around the seeds. The active fractions were separated using gel filtration and HPLC. The aqueous fraction (110 000 xg supernatant) of tomatoes containing anti-platelet activity was subjected to gel filtration column chromatography (Biogel P2 column). The activity was fractionated into two peaks, peak-3 and peak-4 (major peak). Subsequently, peak-4 was further purified by HPLC using a reversed-phase column. NMR and mass spectroscopy studies indicated that peak F2 (obtained from peak 4) contained adenosine and cytidine. Deamination of peak F2 with adenosine deaminase almost completely abolished its anti-platelet activity, confirming the presence of adenosine in this fraction. In comparison, deamination of peak-4 resulted in only partial loss of inhibitory activity while the activity of peak-3 remained unaffected. These results indicate that tomatoes contain anti-platelet compounds in addition to adenosine. Unlike aspirin, the tomato-derived compounds inhibit thrombin-induced platelet aggregation. All these data indicate that tomato contains very potent anti-platelet components, and consuming tomatoes might be beneficial both as a preventive and therapeutic regime for cardiovascular disease.

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Alzheimer's disease is a devastating neurodegenerative disease with a dramatically increasing prevalence and no disease-modifying treatment. Inflammatory lifestyle factors increase the risk of developing Alzheimer's disease. Zinc deficiency is the most prevalent malnutrition in the world and may be a risk factor for Alzheimer's disease potentially through enhanced inflammation, although evidence for this is limited. Here we provide epidemiological evidence suggesting that zinc supplementation was associated with reduced risk and slower cognitive decline, in people with Alzheimer's disease and mild cognitive impairment. Using the APP/PS1 mouse model of Alzheimer's disease fed a control (35 mg/kg zinc) or diet deficient in zinc (3 mg/kg zinc), we determined that zinc deficiency accelerated Alzheimer's-like memory deficits without modifying amyloid β plaque burden in the brains of male mice. The NLRP3-inflammasome complex is one of the most important regulators of inflammation, and we show here that zinc deficiency in immune cells, including microglia, potentiated NLRP3 responses to inflammatory stimuli in vitro , including amyloid oligomers, while zinc supplementation inhibited NLRP3 activation. APP/PS1 mice deficient in NLRP3 were protected against the accelerated cognitive decline with zinc deficiency. Collectively, this research suggests that zinc status is linked to inflammatory reactivity and may be modified in people to reduce the risk and slow the progression of Alzheimer's disease. SIGNIFICANCE STATEMENT Alzheimer's disease is a common condition mostly affecting the elderly. Zinc deficiency is also a global problem, especially in the elderly and also in people with Alzheimer's disease. Zinc deficiency contributes to many clinical disorders, including immune dysfunction. Inflammation is known to contribute to the risk and progression of Alzheimer's disease; thus, we hypothesized that zinc status would affect Alzheimer's disease progression. Here we show that zinc supplementation reduced the prevalence and symptomatic decline in people with Alzheimer's disease. In an animal model of Alzheimer's disease, zinc deficiency worsened cognitive decline because of an enhancement in NLRP3-driven inflammation. Overall, our data suggest that zinc status affects Alzheimer's disease progression, and that zinc supplementation could slow the rate of cognitive decline.

Human zinc deficiency is a global problem and may influence the development of cardiovascular disease. Our objective was to determine Zn deficiency affected pathways and protein interactions in rat aorta and their likely influence on stress-induced atherogenesis. In two separate studies, rats were given diets acutely (<1 mg Zn/kg) or marginally (6 mg Zn/kg) deficient in Zn. Both studies included Zn adequate controls (35 mg Zn/kg) and the acute deficiency study included a pair-fed group. After 6 wk, proteins from thoracic aorta were separated by 2-DE. Proteins affected by zinc deficiency were identified by principal component analysis. Multiple correlations of identified proteins indicated protein networks of related function. Proteins clusters decreased in zinc deficiency were related to fatty acid and carbohydrate metabolism. Structurally related proteins, including zyxin and over nine transgelin 1 proteins, were either increased or decreased by acute and marginal deficiencies. PKC alpha was significantly decreased in Zn deficiency suggesting that Zn may regulate the phosphorylation of target proteins. Zn deficiency-related changes in structural, carbohydrate and fatty acid-related proteins may be disadvantageous for maintaining vascular health and are consistent with a protective role for zinc in the development of atherosclerosis.