The Hepatic Fate of Vitamin E

Vitamin E is a lipophilic vitamin and thus is naturally occurring mainly in high-fat plant products such as oils, nuts, germs, seeds, and in lower amounts in vegetables and some fruits. The term “vitamin E” comprises different structures that are classified as tocopherols, tocotrienols, and “vitamin E-related structures.” Vitamin E follows the same route in the body like other lipophilic substances. In brief, vitamin E is absorbed in the intestine, packaged into chylomicrons together with other lipophilic molecules, and distributed via lymph and blood in the body. As the liver is the central organ in lipoprotein metabolism, it is also essential for the uptake, distribution, metabolism, and storage of vitamin E. Based on the current knowledge on that field, the physiological, nonphysiological, and pathophysiological factors influencing the hepatic handling of vitamin E, verifying the crucial role of the liver in vitamin E homeostasis, are described

Lithium Content of 160 Beverages and Its Impact on Lithium Status in Drosophila melanogaster

Lithium (Li) is an important micronutrient in human nutrition, although its exact molecular function as a potential essential trace element has not yet been fully elucidated. It has been previously shown that several mineral waters are rich and highly bioavailable sources of Li for human consumption. Nevertheless, little is known about the extent in which other beverages contribute to the dietary Li supply. To this end, the Li content of 160 different beverages comprising wine and beer, soft and energy drinks and tea and coffee infusions was analysed by inductively coupled plasma mass spectrometry (ICP-MS). Furthermore, a feeding study in Drosophila melanogaster was conducted to test whether Li derived from selected beverages changes Li status in flies. In comparison to the average Li concentration in mineral waters (108 µg/L; reference value), the Li concentration in wine (11.6 ± 1.97 µg/L) and beer (8.5 ± 0.77 µg/L), soft and energy drinks (10.2 ± 2.95 µg/L), tea (2.8 ± 0.65 µg/L) and coffee (0.1 ± 0.02 µg/L) infusions was considerably lower. Only Li-rich mineral water (~1600 µg/L) significantly increased Li concentrations in male and female flies. Unlike mineral water, most wine and beer, soft and energy drink and tea and coffee samples were rather Li-poor food items and thus may only contribute to a moderate extent to the dietary Li supply. A novelty of this study is that it relates analytical Li concentrations in beverages to Li whole body retention in Drosophila melanogaster

Resveratrol Modulates Desaturase Expression and Fatty Acid Composition of Cultured Hepatocytes

This study aimed to evaluate whether resveratrol (RSV) and its microbial metabolites dihydro-resveratrol (DHR) and lunularin (LUN) affected fatty acid metabolism and omega-3 polyunsaturated fatty acid (n3-PUFA) synthesis in cultured hepatocytes. To this end, cultured human HepG2 hepatocytes were treated with non-toxic concentrations of these polyphenols (40 μM) and Δ5- and Δ6-desaturase (FADS1 and FADS2, respectively) expression was measured. Resveratrol induced both genes but DHR and LUN showed no effect. Co-incubation of RSV with α-linolenic acid (ALA) also induced FADS1 and FADS2 expression. Moreover, transcription of carnitine palmitoyltransferase 1A and fatty acid synthase expression was increased, indicating induction of β-oxidation and fatty acid synthesis, respectively. Using gas chromatography to measure fatty acid levels, we observed the impact of RSV with and without ALA treatment on fatty acid composition. However, RSV reduced unsaturated while increasing saturated fatty acid levels. We found lower amounts of monounsaturated fatty acids (16:1n-7c, 18:1n-9c, 18:1n7c, and 20:1n-9) and n3-PUFA docosahexaenoic acid whereas unsaturated fatty acid levels, especially of stearic acid, were elevated. Of interest, once we co-incubated the cells with RSV together with bovine serum albumin, we found no differences in gene expression compared to cells without RSV treatment. Although we found no positive effect of RSV on n3-PUFA synthesis, the stilbene could possibly prevent cellular stress by decreasing unsaturated fatty acid levels

Boron Contents of German Mineral and Medicinal Waters and Their Bioavailability in Drosophila melanogaster and Humans

Scope Boron is a trace element that naturally occurs in soil, making mineral and medicinal water important contributors to overall intake. Thus, in a systematic screening, the mean boron concentrations of 381 German mineral and medicinal waters are determined. Methods and results Boron concentrations in mineral and medicinal waters are analyzed by inductively coupled mass spectrometry (ICP-MS). Highest boron values find in waters from the southwest of Germany. The boron content of the waters is positively correlated with the concentration of most other analyzed bulk elements, including calcium, potassium, magnesium, and sodium. Mineral waters with either low (7.9 µg L-1 ), medium (113.9 µg L-1 ), or high (2193.3 µg L-1 ) boron content are chosen for boron exposure experiments in fruit flies (Drosophila melanogaster) and humans. In flies, boron-rich mineral water significantly increases boron accumulation, with the accumulation predominantly occurring in the exoskeleton. In humans, serum boron and 24-h urinary boron excretion significantly increase only in response to the intake of boron-rich mineral water. Conclusion Overall, the current data demonstrate that mineral and medicinal waters vary substantially in the content of boron and that boron-rich mineral water can be used to elevate the boron status, both in flies and humans

Variable Expression of Cre Recombinase Transgenes Precludes Reliable Prediction of Tissue-Specific Gene Disruption by Tail-Biopsy Genotyping

The Cre/loxP-system has become the system of choice for the generation of conditional so-called knockout mouse strains, i.e. the tissue-specific disruption of expression of a certain target gene. We here report the loss of expression of Cre recombinase in a transgenic mouse strain with increasing number of generations. This eventually led to the complete abrogation of gene expression of the inserted Cre cDNA while still being detectable at the genomic level. Conversely, loss of Cre expression caused an incomplete or even complete lack of disruption for the protein under investigation. As Cre expression in the tissue of interest in most cases cannot be addressed in vivo during the course of a study, our findings implicate the possibility that individual tail-biopsy genotypes may not necessarily indicate the presence or absence of gene disruption. This indicates that sustained post hoc analyses in regards to efficacy of disruption for every single study group member may be required

Struktur, Metabolismus und biologische Funktion von Vitamin E- und Selen-Derivaten

Die vorliegende Schrift basiert auf elf Manuskripten, welche sich mit dem Metabolismus von Vitamin E und Selen sowie den krebspräventiven Eigenschaften von Derivaten dieser Substanzenklassen befassen. Anhand der Evidenz aus epidemiologischen Studien sowie aus Interventionsstudien konnte ein Zusammenhang zwischen der täglichen Selenaufnahme und verschiedenen Krebsarten hergestellt werden. Ähnliche Ergebnisse hat man für Vitamin E erhalten, jedoch mit geringerer Signifikanz. Aus diesen Studien heraus und durch Erforschung der physiologischen Eigenschaften der beiden Substanzklassen, wurde die SELECT-Studie angelegt. In dieser randomisierten, doppelt-blinden und placebokontrollierten Phase III-Studie soll der Effekt einer Supplementierung mit Selen (200 μg Selenomethionin) und Vitamin E (400 mg DL-α-Tocopherol), jeweils allein und in Kombination, in der Prävention von Prostatakrebs getestet werden (Klein 2004). Die Studie wird unter 32400 Freiwilligen durchgeführt und die letzten Resultate werden 2013 erwartet. Der Habilitand konnte zur Aufklärung des Metabolismus beider Substanzklassen beitragen. In einer Interventionsstudie aus den 90er Jahren wurde Selenhefe verwendet, ohne ihre genaue selenorganische Zusammensetzung zu kennen (Clark, Combs et al. 1996). Erst durch die Arbeiten des Autors wurden die Haupt-und Nebenbestandteile bekannt (Manuskripte 1-3). Der Autor untersuchte sowohl die chemopräventiven Eigenschaften von synthetischen Selenocysteinderivaten als auch von selenangereicherten Pflanzen (Knoblauch) und Selenhefe Manuskripte 3 und 4). Effektiver als die Selenhefe war dabei der Selenknoblauch, der vor allem Se-Methylselenocystein enthielt, eine der am stärksten Apoptose-induzierenden selenorganischen Verbindungen. Derzeit wird eine Interventionsstudie mit Se-Methylselenocystein bei Brustkrebspatienten unter Leitung von Clement Ip (Roswell Park Cancer Institute, Buffalo NY, USA) vorbereitet. Eine kürzlich erschienene Follow-Up-Studie des NPC-trials zeigte einen positiven Einfluss des Selens auf die Kolorektaltumor-Inzidenz. In diesem Zusammenhang scheint das Manuskript 5 interessant, da der Autor den Einfluss der intestinalen Flora auf die Bio-aktivierung von Se-Methylselenocystein zeigen konnte

Strategic framing of genome editing in agriculture: an analysis of the debate in Germany in the run-up to the European Court of Justice ruling

Gefördert im Rahmen des Projekts DEA