TY - THES A1 - Blum, Claudia T1 - Biosynthese und Zielsteuerung von TAS2R-Bitterrezeptoren Y1 - 2010 CY - Potsdam ER - TY - JOUR A1 - Bobbert, Thomas A1 - Raila, Jens A1 - Schwarz, Franziska A1 - Mai, Knut A1 - Henze, Andrea A1 - Pfeiffer, Andreas F. H. A1 - Schweigert, Florian J. A1 - Spranger, Joachim T1 - Relation between retinol, retinol-binding protein 4, transthyretin and carotid intima media thickness N2 - Objective: Retinol is transported in a complex with retinol-binding protein 4 (RBP4) and transthyretin (TTR) in the circulation. While retinol is associated with various cardiovascular risk factors, the relation between retinol, RBP4, TTR and carotid intima media thickness (IMT) has not been analysed yet. Methods: Retinol, RBP4 and TTR were measured in 96 individuals and their relation to mean and maximal IMT was determined. Results: Mean IMT correlated with RBP4 (r = 0.335, p < 0.001), retinol (r = -0.241, p = 0.043), RBP/TTR ratio (r = 0.254, p = 0.025) and retinol/RBP4 ratio (r = -0.549, p < 0.001). Adjustment for age, sex, BMI, blood pressure, HDL/total cholesterol ratio, triglyceride, diabetes and smoking revealed that the retinol/RBP4 ratio was strongly and independently associated with mean IMT. Similar results were found for maximal IMT, which included the measurement of plaques. Conclusion: The data support that the transport complex of vitamin A is associated with the IMT, an established parameter of atherosclerosis. Changes in RBP4 saturation with retinol may link renal dysfunction and insulin resistance to atherosclerosis. Y1 - 2010 UR - http://www.sciencedirect.com/science/journal/00219150 U6 - https://doi.org/10.1016/j.atherosclerosis.2010.07.063 SN - 0021-9150 ER - TY - JOUR A1 - Braune, Annett A1 - Maul, Ronald A1 - Schebb, Nils Helge A1 - Kulling, Sabine E. A1 - Blaut, Michael T1 - The red clover isoflavone irilone is largely resistant to degradation by the human gut microbiota N2 - Intestinal bacteria may influence bioavailability and physiological activity of dietary isoflavones. We therefore investigated the ability of human intestinal microbiota to convert irilone and genistein in vitro. In contrast to genistein, irilone was largely resistant to transformation by fecal slurries of ten human subjects. The fecal microbiota converted genistein to dihydrogenistein, 6'-hydroxy-O-desmethylangolensin, and 2-(4-hydroxyphenyl)- propionic acid. However, considerable interindividual differences in the rate of genistein degradation and the pattern of metabolites formed from genistein were observed. Only one metabolite, namely dihydroirilone, was formed from irilone in minor amounts. In further experiments, Eubacterium ramulus, a prevalent flavonoid-degrading species of the human gut, was tested for transformation of irilone. In contrast to genistein, irilone was not converted by E. ramulus. Irilone only differs from genistein by a methylenedioxy group attached to the A-ring of the isoflavone skeleton. This substitution obviously restricts the degradability of irilone by human intestinal bacteria. Y1 - 2010 UR - http://www3.interscience.wiley.com/cgi-bin/jhome/109582333 U6 - https://doi.org/10.1002/mnfr.200900233 SN - 1613-4125 ER - TY - JOUR A1 - Carlsohn, Anja A1 - Rohn, Sascha A1 - Mayer, Frank A1 - Schweigert, Florian J. T1 - Physical activity, antioxidant status, and protein modification in adolescent athletes N2 - Exercise may increase reactive oxygen species production, which might impair cell integrity and contractile function of muscle cells. However, little is known about the effect of regular exercise on the antioxidant status of adolescents. Purpose: This study aimed to evaluate the impact of exercise on the antioxidant status and protein modifications in adolescent athletes. Methods: In 90 athletes and 18 controls (16 +/- 2 yr), exercise-related energy expenditure was calculated on the basis of a 7-d activity protocol. Antioxidant intake and plasma concentrations of alpha-tocopherol, carotenoids, and uric acid were analyzed. Plasma antioxidant activity was determined by Trolox equivalent (TE) antioxidant capacity and electron spin resonance spectrometry. Protein modifications were assessed with structural changes of transthyretin using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Data were analyzed by two-way ANOVA and post hoc by the Tukey-Kramer test (alpha = 0.05). Results: Antioxidant intake correlated with energy intake and was within the recommended daily allowance for vitamins C and E and beta-carotene. Plasma levels of neither nutritional antioxidants nor uric acid differed between the groups. TE antioxidant capacity was higher in athletes (men = 1.47 perpendicular to 0.2 mmol TE per liter, women = 1.45 perpendicular to 0.2 mmol TE per liter) compared with controls (men = 1.17 +/- 0.04 mmol TE per liter, women = 1.14 +/- 0.04 mmol TE per liter) and increased with exercise-related energy expenditure (P = 0.007). Transthyretin cysteinylation rate differed between the groups, with the highest rate of protein modifications in moderately active subjects (P = 0.007). Conclusions: Results suggest that if the nutritional choice of athletes is well balanced, enough antioxidants are provided to meet recommended amounts. Moreover, regular exercise increases blood antioxidant capacity in young athletes, whereas chronic exercise was not shown to promote protein modifications. Thus, in young athletes who are sufficiently supplied with antioxidants, beneficial effects of exercise on antioxidant status rather than on oxidative stress may be anticipated. Y1 - 2010 UR - http://www.ms-se.com/ U6 - https://doi.org/10.1249/Mss.0b013e3181c74f7b SN - 0195-9131 ER - TY - JOUR A1 - Eggert, Kai A1 - Hollmann, Juergen A1 - Hiller, Beate A1 - Kruse, Hans-Peter A1 - Rawel, Harshadrai Manilal A1 - Pawelzik, Elke T1 - Effects of Fusarium infection on the phenolics in emmer and naked barley N2 - Inoculated or non-inoculated naked barley and emmer cultivars were investigated with regard to their influence on phenolic acid profiles and their arabinoxylan content. Two groups of phenolic compounds were differentiated-methanol- soluble and hydrolyzable covalent-bound phenolic compounds. Chromatographic methods were applied for their analysis. The results showed ferulic acid as the predominant phenol in both total and covalent-bound fractions. The inoculation significantly reduced the ferulic acid content within a range of 5.6-6.6% in the two cereals and all their cultivars. Naked barley cultivars additionally contained the flavonoid catechin in the soluble fraction. The innoculation led here to a significant increase in the catechin content of about 4.5%. These results document an induction of the synthesis of catechin in naked barley after artificial Fusarium infection, whereas the ferulic acid content declined. Y1 - 2010 UR - http://pubs.acs.org/journal/jafcau U6 - https://doi.org/10.1021/Jf903545j SN - 0021-8561 ER - TY - JOUR A1 - Fischer, Stephanie S. A1 - Kempe, Daniela S. A1 - Leibrock, Christina B. A1 - Rexhepaj, Rexhep A1 - Siraskar, Balasaheb A1 - Boini, Krishna M. A1 - Ackermann, Teresa F. A1 - Foeller, Michael A1 - Hocher, Berthold A1 - Rosenblatt, Kevin P. A1 - Kuro-o, Makoto A1 - Lang, Florian T1 - Hyperaldosteronism in Klotho-deficient mice N2 - Klotho is a membrane protein participating in the inhibitory effect of FGF23 on the formation of 1,25- dihydroxyvitamin-D-3 [1,25(OH)(2)D-3]. It participates in the regulation of renal tubular phosphate reabsorption and stimulates renal tubular Ca2+ reabsorption. Klotho hypomorphic mice (klotho(hm)) suffer from severe growth deficit, rapid aging, and early death, events largely reversed by a vitamin D-deficient diet. The present study explored the role of Klotho deficiency in mineral and electrolyte metabolism. To this end, klothohm mice and wild-type mice (klotho(+/+)) were subjected to a normal (D+) or vitamin D-deficient (D-) diet or to a vitamin D-deficient diet for 4 wk and then to a normal diet (D-/+). At the age of 8 wk, body weight was significantly lower in klotho(hm)D(+) mice than in klotho(+/ +)D(+) mice, klotho(hm)D(-) mice, and klotho(hm)D(-/+) mice. Plasma concentrations of 1,25(OH)(2)D-3, adrenocorticotropic hormone (ACTH), antidiuretic hormone (ADH), and aldosterone were significantly higher in klotho(hm)D(+) mice than in klotho(+/+)D(+) mice. Plasma volume was significantly smaller in klotho(hm)D(-/+) mice, and plasma urea, Ca2+, phosphate and Na+, but not K+ concentrations were significantly higher in klotho(hm)D(+) mice than in klotho(+/+)D(+) mice. The differences were partially abrogated by a vitamin D-deficient diet. Moreover, the hyperaldosteronism was partially reversed by Ca2+-deficient diet. Ussing chamber experiments revealed a marked increase in amiloride-sensitive current across the colonic epithelium, pointing to enhanced epithelial sodium channel (ENaC) activity. A salt-deficient diet tended to decrease and a salt-rich diet significantly increased the life span of klotho(hm)D(+) mice. In conclusion, the present observation disclose that the excessive formation of 1,25(OH)(2)D-3 in Klotho-deficient mice results in extracellular volume depletion, which significantly contributes to the shortening of life span. Y1 - 2010 UR - http://ajprenal.physiology.org/ U6 - https://doi.org/10.1152/ajprenal.00233.2010 SN - 1931-857X ER - TY - JOUR A1 - Foeller, Michael A1 - Mahmud, Hasan A1 - Qadri, Syed M. A1 - Gu, Shuchen A1 - Braun, Manuel A1 - Bobbala, Diwakar A1 - Hocher, Berthold A1 - Lang, Florian T1 - Endothelin B receptor stimulation inhibits suicidal erythrocyte death N2 - Endothelins (ETs), potent endothelium-derived mediators, stimulate formation of nitric oxide, which, in turn, protects against suicidal erythrocyte death or eryptosis, characterized by phosphatidylserine exposure at the erythrocyte surface and triggered by increase in cytosolic Ca2+ ([Ca2+](i)). The present study explored whether the ET1- receptor ETB influences suicidal erythrocyte death. To this end, [Ca2+](i) (Fluo3-fluorescence) and phosphatidylserine exposure (annexin V-binding) were determined utilizing FACS analysis. Energy depletion increased [Ca2+]i and phosphatidylserine-exposure, effects significantly blunted by ET1 (IC50 approximate to 100 nM) and the ETB receptor- agonist sarafotoxin 6c (IC50 approximate to 10 nM) but not by ET2 and ET3. ET1 and sarafotoxin significantly delayed the kinetics of suicidal erythrocyte death following energy depletion. ETB stimulation did not blunt the effect of Ca2+- ionophore ionomycin (1 mu M) on phosphatidylserine exposure. The in vivo significance was tested using rescued ETB- knockout (etb(-/-)) and wild-type (etb(+/+)) mice. The number of phosphatidylserine-exposing erythrocytes, of reticulocytes and spleen size were significantly larger in etb(-/-) mice than in etb(+/+)-mice. The etb(-/-) erythrocytes were more susceptible to the eryptotic effect of oxidative stress and more rapidly cleared from circulating blood than etb(+/+) erythrocytes. Finally, the spleens from etb(-/-) mice were enlarged and contained markedly more phosphatidylserine- exposing erythrocytes than spleens from etb(+/+) mice. The observations disclose a novel function of ET1, i. e., protection from suicidal erythrocyte death. Y1 - 2010 UR - http://www.fasebj.org/ U6 - https://doi.org/10.1096/Fj.10-159483 SN - 0892-6638 ER - TY - THES A1 - Friedrich, Maika T1 - Wirkung von Teecatechin Epigallocatechingallat auf den Energiestoffwechsel der Maus T1 - Effect of tea catechin epigallocatechin gallate on energy metabolism in mice N2 - Die gesundheitsfördernden Eigenschaften von grünem Tee sind weitgehend akzeptiert. Den Teecatechinen, insbesondere dem Epigallocatechin-3-gallat (EGCG), werden zahlreiche positive Effekte zugesprochen (z. B. antioxidativ, antikanzerogen, antiinflammatorisch, Blutdruck und Cholesterinspiegel senkend). Die Mechanismen, die zu einer Reduktion der in Tierversuchen beschriebenen Körper- und Fettmasse führen, sind nicht ausreichend geklärt. Ziel dieser Arbeit bestand darin, die kurz- und mittelfristigen Wirkungen einer TEAVIGO®-Applikation (mind. 94 % EGCG) am Mausmodell im Hinblick auf den Energie- und Fettstoffwechsel sowie die Expression daran beteiligter Gene in wichtigen Organen und Geweben zu untersuchen. In verschiedenen Tierversuchen wurde männlichen C57BL/6-Mäusen eine Hochfettdiät (HFD) mit und ohne Supplementation (oral, diätetisch) des entkoffeinierten Grüntee-Extraktes TEAVIGO® in unterschiedlichen Dosierungen gefüttert. Es wurden sowohl kurz- als auch mittelfristige Wirkungen des EGCG auf die Energiebilanz (u. a. indirekte Tierkalorimetrie) und Körperzusammensetzung (NMR) sowie die exogene Substratoxidation (Stabilisotopentechnik: Atemtests, Inkorporation natürlicher 13C-angereicherter Triglyceride aus Maiskeimöl in diverse Organe/Gewebe) und Gen-expression (quantitative real-time PCR) untersucht. Die Applikationsform und ihre Dauer riefen unterschiedliche Wirkungen hervor. Mäuse mit diätetischer Supplementation zeigten bereits nach kurzer Zeit eine verminderte Körperfettmasse, die bei weiterer Verabreichung auch zu einer Reduktion der Körpermasse führte. Beide Applikationsformen resultieren, unabhängig von der Dauer der Intervention, in einer erhöhten Energieausscheidung, während die Futter- und Energieaufnahme durch EGCG nicht beeinflusst wurden. Der Energieverlust war von einer erhöhten Fett- und Stickstoffausscheidung begleitet, deren Ursache die in der Literatur beschriebene Interaktion und Hemmung digestiver Enzyme sein könnte. Besonders unter postprandialen Bedingungen wiesen EGCG-Mäuse erniedrigte Triglycerid- und Glycogengehalte in der Leber auf, was auf eine eingeschränkte intestinale Absorption der Nährstoffe hindeutet. Transkriptanalysen ergaben im Darm eine verminderte Expression von Fettsäuretransportern, während die Expression von Glucosetransportern durch EGCG erhöht wurde. Weiterhin reduzierte EGCG, nach Umstellung von Standard- auf eine maiskeimölhaltige Hochfettdiät, die Inkorporation natürlicher 13C-angereicherter Triglyceride in diverse Organe und Gewebe – insbesondere Leber, viszerales und braunes Fettgewebe sowie Skelettmuskel. Die Analyse der 13C-Anreicherung im Atem der Mäuse und die Energieumsatzmessungen ergaben nach kurzer Applikation eine erhöhte Fettoxidation, die im weiteren Verlauf der Intervention auf eine erhöhte Kohlenhydratoxidation umgeschaltet wurde. Weiterhin war die orale Applikation von EGCG bei gleichzeitiger Fütterung einer Hochfettdiät von makroskopischen und mikroskopischen degenerativen Veränderungen der Leber begleitet. Diese Effekte wurden nach diätetischer Supplementation der Hochfettdiät mit EGCG nicht beobachtet. Zusammenfassend zeigen die Ergebnisse, dass die Körpergewichts- und Fettgewebs-abnahme durch diätetisches EGCG sich durch eine herabgesetzte Verdaulichkeit der Nahrung erklären lässt. Dies führte zu verschiedenen kurz- und mittelfristigen Veränderungen in der Fettverteilung und im Fettmetabolismus. N2 - The health-promoting properties of green tea are widely accepted. Tea catechins, particularly epigallocatechin-3-gallate (EGCG), are attributed to many positive effects (anti-oxidative, anti-cancerogen, anti-inflammatory, blood pressure and cholesterol lowering). Mechanisms leading to a reduction of body mass and fat mass in animal experiments are not fully elucidated. The aim of this study was to examine multiple effects of TEAVIGO® application (at least 94% EGCG) in a mouse model in terms of energy and fat metabolism. Expressions of genes involved in these processes were also determined in different organs and tissues. In several animal studies, male C57BL/6 mice were fed a high fat diet supplemented with decaffeinated TEAVIGO® (oral, dietetic) at different dosages. Short- and medium-term effects of EGCG were investigated on energy balance (indirect animal calorimetry), body composition (NMR), exogenous substrate oxidation (stable isotopes: breath tests, incorporation of naturally 13C-enriched triglycerides from corn oil into various organs/tissues), and gene expression (quantitative real-time PCR). Type of application and its duration elicited different effects. Supplemented mice already showed a reduced body fat mass after short- and medium-term treatment. Further administration lead to a reduction of body weight. Regardless of the duration of intervention, both types of application resulted in an increased energy excretion, while food and energy intake was not affected by EGCG. Fecal energy loss was accompanied by an increased fat and nitrogen excretion, which was probably due to an inhibition of digestive enzymes. Fed mice displayed a decreased triglyceride and glycogen content in liver suggesting a reduced absorption of nutrients in the intestine. This was supported by a decreased expression of intestinal fatty acid transporters. However, expression of glucose transporters was increased after short- and medium term application. Furthermore, EGCG attenuated incorporation of naturally 13C-enriched triglycerides into various organs and tissues – particularly liver, visceral and brown adipose tissue, and skeletal muscle. Analysis of 13C-enrichment in breath and measurement of energy expenditure revealed an initial increased fat oxidation, which was switched to an increased carbohydrate oxidation over time. Besides, a combination of oral administration of EGCG and high fat feeding was accompanied by macroscopic and microscopic deleterious changes in liver. These effects were not observed after dietary supplementation of EGCG. Altogether, reduction in body mass and fat mass by EGCG can be explained by a decreased food digestibility leading to various short- and medium-term changes in fat distribution and lipid metabolism. KW - Grüner Tee KW - Teecatechin KW - Epigallocatechingallat KW - Energiestoffwechsel KW - Fettstoffwechsel KW - green tea KW - tea catechin KW - epigallocatechin gallate KW - energy metabolism KW - fat metabolism Y1 - 2010 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-48159 ER - TY - JOUR A1 - Fritzsche, Britta A1 - Schuchardt, Jan-Philipp A1 - Schmidt, Anja A1 - Nau, Heinz A1 - Schweigert, Florian J. A1 - Ruehl, Ralph T1 - CYP26A1-specific antagonist influence on embryonic implantation, gene expression and endogenous retinoid concentration in rats N2 - Retinoids are essential in vertebrate reproduction and embryonic development. All-trans-retinoic acid (ATRA) is tightly regulated during these processes. CYP26A1 is mainly responsible for its degradation. To study the role of CYP26A1 during implantation, we applied R115866, a CYP26A1-specific antagonist, to rats during early gestation days (GD). On GD 6.5 and 12 samples were collected and the number of embryos was evaluated. ATRA concentration increased in uterus and serum, mRNA expression of CYP26A1 and CRABP2 increased in the liver, but not in the uterus. Uterine COX1 and 17 beta HSD mRNA expression was decreased. The number of embryos on GD 12 was not altered in this setting. It can be concluded that uterine expression of the analyzed retinoid-response genes during early gestation is not altered by this R115866 treatment and instead indirectly via ATRA. From our experiment we cannot confirm that ATRA obtains a major influencing role in the regulation of embryonic implantation. Y1 - 2010 UR - http://www.sciencedirect.com/science/journal/08906238 U6 - https://doi.org/10.1016/j.reprotox.2010.05.005 SN - 0890-6238 ER - TY - THES A1 - Gerber, Chimgee Baasanjav T1 - Detection and identification of genotoxicant from brassica plants Y1 - 2010 CY - Potsdam ER -