Apolipoprotein E genotype, vitamin E, and Alzheimer’s disease prevention

Alzheimer’s disease (AD) is a multi-causal neurodegenerative disorder and the most common form of dementia in the elderly. Although extensively investigated, the exact underlying molecular and cellular mechanisms of AD remain to be fully elucidated. Amongst other factors, AD may be associated with increased oxidative stress and chronic inflammation. Although dietary antioxidants, in particular vitamin E, have been related to a reduction of AD risk, data from clinical studies are still contradictory. Aside from increasing age, one key risk factor for sporadic AD is the apolipoprotein E4 genotype. As major component of lipoproteins the apolipoprotein E (apoE) is of crucial importance in the distribution of cholesterol and lipids within the brain and thus, involved in neuronal membrane repair mechanisms. However, apoE4 has been associated with several altered cellular features including an impaired neuronal repair function and a higher neuronal vulnerability towards oxidative insults leading to an increased AD risk. In this context, the role of antioxidant supplementation as a primary prevention strategy for subjects at high risk including carriers of the apoε4 allele, is discussed

Historical Reflection of Food Processing and the Role of Legumes as Part of a Healthy Balanced Diet

The purpose of food processing has changed over time. High-intensity industrially processed food often exhibits higher concentrations of added sugar, salt, higher energy, and lower micronutrient density than does similar food or meals prepared at home from raw or minimally processed food. Viewing the evolution of food processing from history, one could make out three major transitions related to human socioeconomic changes. The first transition was marked by the change from hunting and gathering to settled societies with agriculture and livestock farming. The second and third transitions were associated with the Industrial Revolution and with market liberalization, global trade and automation, respectively. The next major transition that will influence food processing and shape human nutrition may include the exploitation of sustainable and efficient protein and food sources that will ensure high-quality food production for the growing world population. Apart from novel food sources, traditional food such as legumes and pulses likewise exhibit great potential to contribute to a healthy balanced diet. The promotion of legumes should be intensified in public dietary guidelines because their consumption is rather low in high-income countries and increasingly displaced as a traditional staple by industrially processed food in low- to middle-income countries

Taurine Enhances Iron-Related Proteins and Reduces Lipid Peroxidation in Differentiated C2C12 Myotubes

Taurine is a nonproteinogenic amino sulfonic acid in mammals. Interestingly, skeletal muscle is unable to synthesize taurine endogenously, and the processing of muscular taurine changes throughout ageing and under specific pathophysiological conditions, such as muscular dystrophy. Ageing and disease are also associated with altered iron metabolism, especially when there is an excess of labile iron. The present study addresses the question of whether taurine connects cytoprotective effects and redox homeostasis in a previously unknown iron-dependent manner. Using cultured differentiated C2C12 myotubes, the impact of taurine on markers of lipid peroxidation, redox-sensitive enzymes and iron-related proteins was studied. Significant increases in the heme protein myoglobin and the iron storage protein ferritin were observed in response to taurine treatment. Taurine supplementation reduced lipid peroxidation and BODIPY oxidation by ~60 and 25%, respectively. Furthermore, the mRNA levels of redox-sensitive heme oxygenase (Hmox1), catalase (Cat) and glutamate-cysteine ligase (Gclc) and the total cellular glutathione content were lower in taurine-supplemented cells than they were in the control cells. We suggest that taurine may inhibit the initiation and propagation of lipid peroxidation by lowering basal levels of cellular stress, perhaps through reduction of the cellular labile iron pool

Curcumin may impair iron status when fed to mice for six months

AbstractCurcumin has been shown to have many potentially health beneficial properties in vitro and in animal models with clinical studies on the toxicity of curcumin reporting no major side effects. However, curcumin may chelate dietary trace elements and could thus potentially exert adverse effects. Here, we investigated the effects of a 6 month dietary supplementation with 0.2% curcumin on iron, zinc, and copper status in C57BL/6J mice. Compared to non-supplemented control mice, we observed a significant reduction in iron, but not zinc and copper stores, in the liver and the spleen, as well as strongly suppressed liver hepcidin and ferritin expression in the curcumin-supplemented mice. The expression of the iron-importing transport proteins divalent metal transporter 1 and transferrin receptor 1 was induced, while hepatic and splenic inflammatory markers were not affected in the curcumin-fed mice. The mRNA expression of other putative target genes of curcumin, including the nuclear factor (erythroid-derived 2)-like 2 and haem oxygenase 1 did not differ between the groups. Most of the published animal trials with curcumin-feeding have not reported adverse effects on iron status or the spleen. However, it is possible that long-term curcumin supplementation and a Western-type diet may aggravate iron deficiency. Therefore, our findings show that further studies are needed to evaluate the effect of curcumin supplementation on iron status

Apolipoprotein E genotype and hepatitis C, HIV and herpes simplex disease risk: a literature review

Apolipoprotein E is a polymorphic and multifunctional protein with numerous roles in lipoprotein metabolism. The three common isoforms apoE2, apoE3 and apoE4 show isoform-specific functional properties including different susceptibilities to diseases. ApoE4 is an accepted risk factor for Alzheimer's disease and cardiovascular disorders. Recently, associations between apoE4 and infectious diseases have been demonstrated. This review summarises how apoE4 may be involved in the infection incidence and associated pathologies of specific infectious diseases, namely hepatitis C, human immunodeficiency virus disease and herpes simplex

Anti-Inflammatory Properties of Brazilian Green Propolis Encapsulated in a γ-Cyclodextrin Complex in Mice Fed a Western-Type Diet

Ageing is often accompanied by chronic inflammation. A fat- and sugar-rich Western-type diet (WTD) may accelerate the ageing phenotype. Cell culture studies have indicated that artepillin C-containing Brazilian green propolis exhibits anti-inflammatory properties. However, little is known regarding its anti-inflammatory potential in mouse liver in vivo. In this study, female C57BL/6NRj wild-type mice were fed a WTD, a WTD supplemented with Brazilian green propolis supercritical extract (GPSE) encapsulated in γ-cyclodextrin (γCD) or a WTD plus γCD for 10 weeks. GPSE-γCD did not affect the food intake, body weight or body composition of the mice. However, mRNA levels of the tumour necrosis factor α were significantly downregulated (p < 0.05) in these mice compared to those in the WTD-fed controls. Furthermore, the gene expression levels of other pro-inflammatory markers, including serum amyloid P, were significantly (p < 0.001) decreased following GPSE-γCD treatment. GPSE-γCD significantly induced hepatic ferritin gene expression (p < 0.01), which may contribute to its anti-inflammatory properties. Conversely, GPSE-γCD did not affect the biomarkers of endogenous antioxidant defence, including catalase, glutathione peroxidase-4, paraoxonase-1, glutamate cysteine ligase and nuclear factor erythroid 2-related factor-2 (Nrf2). Overall, the present data suggest that dietary GPSE-γCD exhibits anti-inflammatory, but not antioxidant activity in mouse liver in vivo. Thus, GPSE-γCD has the potential to serve as a natural hepatoprotective bioactive compound for dietary-mediated strategies against chronic inflammation

Apolipoprotein E (APOE) genotype regulates body weight and fatty acid utilization—Studies in gene-targeted replacement mice

Scope Of the three human apolipoprotein E (APOE) alleles, the ε3 allele is most common, which may be a result of adaptive evolution. In this study, we investigated whether the APOE genotype affects body weight and energy metabolism through regulation of fatty acid utilization. Methods and results Targeted replacement mice expressing the human APOE3 were significantly heavier on low- and high-fat diets compared to APOE4 mice. Particularly on high-fat feeding, food intake and dietary energy yields as well as fat mass were increased in APOE3 mice. Fatty acid mobilization determined as activation of adipose tissue lipase and fasting plasma nonesterified fatty acid levels were significantly lower in APOE3 than APOE4 mice. APOE4 mice, in contrast, exhibited higher expression of proteins involved in fatty acid oxidation in skeletal muscle. Conclusion Our data suggest that APOE3 is associated with the potential to more efficiently harvest dietary energy and to deposit fat in adipose tissue, while APOE4 carriers tend to increase fatty acid mobilization and utilization as fuel substrates especially under high-fat intake. The different handling of dietary energy may have contributed to the evolution and worldwide distribution of the ε3 allele

Furbellow (Brown Algae) Extract Increases Lifespan in Drosophila by Interfering with TOR-Signaling

Algal products are well known for their health promoting effects. Nonetheless, an in depth understanding of the underlying molecular mechanisms is still only fragmentary. Here, we show that aqueous furbelow extracts (brown algae, Saccorhiza polyschides) lengthen the life of both sexes of the fruit fly Drosophila melanogaster substantially, if used as nutritional additives to conventional food. This life prolonging effect became even more pronounced in the presence of stressors, such as high-fat dieting of living under drought conditions. Application of the extracts did not change food intake, excretion, or other major physiological parameters. Nevertheless, effects on the intestinal microbiota were observed, leading to an increased species richness, which is usually associated with healthy conditions. Lifespan extension was not observed in target of rapamycin (TOR)-deficient animals, implying that functional TOR signaling is necessary to unfold the positive effects of brown algae extract (BAE) on this important trait. The lack of life lengthening in animals with deregulated TOR signaling exclusively targeted to body fat showed that this major energy storage organ is instrumental for transmitting these effects. In addition, expression of Imaginal morphogenesis protein-Late 2 (Imp-L2), an effective inhibitor of insulin signaling implies that BAE exerts their positive effects through interaction with the tightly interwoven TOR- and insulin-signaling systems, although insulin levels were not directly affected by this intervention

A Natural mtDNA Polymorphism in Complex III Is a Modifier of Healthspan in Mice

In this study, we provide experimental evidence that a maternally inherited polymorphism in the mitochondrial cytochrome b gene (mt-Cytb; m.15124A>G, Ile-Val) in mitochondrial complex III resulted in middle-aged obesity and higher susceptibility to diet-induced obesity, as well as age-related inflammatory disease, e.g., ulcerative dermatitis, in mice. As a consequence of the gene variation, we observed alterations in body composition, metabolism and mitochondrial functions, i.e., increased mitochondrial oxygen consumption rate and higher levels of reactive oxygen species, as well as in the commensal bacterial composition in the gut, with higher abundance of Proteobacteria in mice carrying the variant. These observations are in line with the previously described links of the mitochondrial complex III gene with obesity and metabolic diseases in humans. Given that these functional changes by the G variant at m.15124 in the mt-Cytb are already present in young mice that were kept under normal condition, it is plausible that the m.15124A>G variant is a disease susceptibility modifier to the diseases induced by additional stressors, i.e., dietary and/or aging stress, and that the variant results in the higher incidence of clinical diseases presentation in C57BL/6J-mt129S1/SvlmJ than C57BL/6J mice. Thus, mtDNA variants could be potential biomarkers to evaluate the healthspan