TY - JOUR A1 - Zebger-Gong, Hong A1 - Mueller, Dominik A1 - Diercke, Michaela A1 - Haffner, Dieter A1 - Hocher, Berthold A1 - Verberckmoes, Steven A1 - Schmidt, Sven A1 - D'Haese, Patrick C. A1 - Querfeld, Uwe T1 - 1,25-Dihydroxyvitamin D-3-induced aortic calcifications in experimental uremia: up-regulation of osteoblast markers, calcium-transporting proteins and osterix JF - Journal of hypertension N2 - Background and objective Whether treatment with vitamin D receptor activators contributes to cardiovascular disease in patients with chronic kidney disease is a matter of debate. We studied mechanisms involved in vitamin D-related vascular calcifications in vivo and in vitro. Methods Aortic calcifications were induced in subtotally nephrectomized (SNX) rats by treatment with a high dose (0.25 mu g/kg per day) of 1,25-dihydroxyvitamin D-3 (calcitriol) given for 6 weeks. Likewise, primary rat vascular smooth muscle cells (VSMCs) were incubated with calcitriol at concentrations ranging from 10(-11) to 10(-7) mol/l. Immunohistochemistry revealed that the aortic expression of osteopontin, osteocalcin and bone sialoprotein was significantly increased in calcitriol-treated SNX rats compared to untreated SNX controls. In addition, aortic expression of the transient receptor potential vanilloid calcium channel 6 (TRPV6) and calbindin D9k was significantly up-regulated by treatment with calcitriol. Furthermore, calcitriol significantly increased expression of the osteogenic transcription factor osterix. In-vitro studies showed similar results, confirming that these effects could be attributed to treatment with calcitriol. Conclusions High-dose calcitriol treatment induces an osteoblastic phenotype in VSMC both in SNX rats and in vitro, associated with up-regulation of proteins regulating mineralization and calcium transport, and of the osteogenic transcription factor osterix. KW - calbindin D9k KW - calcitriol KW - calcium transport KW - osteoblast KW - osterix KW - TRPV5 KW - TRPV6 KW - vascular calcification Y1 - 2011 U6 - https://doi.org/10.1097/HJH.0b013e328340aa30 SN - 0263-6352 VL - 29 IS - 2 SP - 339 EP - 348 PB - Lippincott Williams & Wilkins CY - Philadelphia ER - TY - JOUR A1 - Yang, Xiaoping A1 - Darko, Kwame Oteng A1 - Huang, Yanjun A1 - He, Caimei A1 - Yang, Huansheng A1 - He, Shanping A1 - Li, Jianzhong A1 - Li, Jian A1 - Hocher, Berthold A1 - Yin, Yulong T1 - Resistant starch regulates gut microbiota BT - structure, biochemistry and cell signalling JF - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology N2 - Starch is one of the most popular nutritional sources for both human and animals. Due to the variation of its nutritional traits and biochemical specificities, starch has been classified into rapidly digestible, slowly digestible and resistant starch. Resistant starch has its own unique chemical structure, and various forms of resistant starch are commercially available. It has been found being a multiple-functional regulator for treating metabolic dysfunction. Different functions of resistant starch such as modulation of the gut microbiota, gut peptides, circulating growth factors, circulating inflammatory mediators have been characterized by animal studies and clinical trials. In this mini-review, recent remarkable progress in resistant starch on gut microbiota, particularly the effect of structure, biochemistry and cell signaling on nutrition has been summarized, with highlights on its regulatory effect on gut microbiota. KW - Resistant starch KW - Gut microbiota KW - Nutrition Y1 - 2017 U6 - https://doi.org/10.1159/000477386 SN - 1015-8987 SN - 1421-9778 VL - 42 IS - 1 SP - 306 EP - 318 PB - Karger CY - Basel ER - TY - JOUR A1 - Yang, Fang A1 - Lai, Xinlong A1 - Deng, Li A1 - Liu, Xiaoxiao A1 - Li, Jian A1 - Zeng, Shuixiu A1 - Zhang, Cheng A1 - Hocher, Carl-Friedrich A1 - Hocher, Berthold T1 - Association of endothelin-1 gene polymorphisms with the clinical phenotype in primary nephrotic syndrome of children JF - Life sciences : molecular, cellular and functional basis of therapy N2 - Aims:This study aims to investigate the relationship between plasma endothelin-1 (ET-1) concentrations, ET-1 gene polymorphisms in loci rs5370, rs1630736, 3A/4A and clinical features of primary nephrotic syndrome (NS) in children. Materials and methods: Thirty-six children with primary NS were selected as case group, and 94 healthy children were selected as control group. All subjects were genotyped for three single nucleotide polymorphisms (SNPs) (rs5370, rs10478694 [3A4A) and rs 1630736) in the ET-1 gene by gene sequencing. The plasma ET-1 concentrations were measured using a radio-immunoassay. Key findings: Plasma ET-1 concentrations were higher in NS patients (P = 0.007) as compared to healthy children. The allele frequencies between control and NS patients were significantly different only with respect to the rs10478694 SNP of the ET-1 gene. The allele frequencies between control and NS patients for the rs5370 SNP showed a trend towards difference (P = 0.057). Plasma cholesterol in NS patients is associated with both: the Cl genotype in locus rs5370 and the 3A4A genotype in locus rs10478694 (P < 0.05 in both cases). Significance: The ET systems might play a disease modifying role in pediatric NS. Plasma cholesterol, a hallmark of NS. seems to be associated with genetic variations within the human ET-1 gene. (C) 2014 Elsevier Inc. All rights reserved. KW - Endothelin-1 KW - Gene polymorphism KW - Childhood nephrotic syndrome KW - Cholesterol Y1 - 2014 U6 - https://doi.org/10.1016/j.lfs.2014.04.010 SN - 0024-3205 SN - 1879-0631 VL - 118 IS - 2 SP - 446 EP - 450 PB - Elsevier CY - Oxford ER - TY - JOUR A1 - Yamamoto, Masayoshi A1 - Baldermann, Susanne A1 - Yoshikawa, Keisuke A1 - Fujita, Akira A1 - Mase, Nobuyuki A1 - Watanabe, Naoharu T1 - Determination of volatile compounds in four commercial samples of japanese green algae using solid phase microextraction gas chromatography mass spectrometry JF - The ScientificWorld journal N2 - Green algae are of great economic importance. Seaweed is consumed fresh or as seasoning in Japan. The commercial value is determined by quality, color, and flavor and is also strongly influenced by the production area. Our research, based on solid phase microextraction gas chromatography mass spectrometry (SPME-GC-MS), has revealed that volatile compounds differ intensely in the four varieties of commercial green algae. Accordingly, 41 major volatile compounds were identified. Heptadecene was the most abundant compound from Okayama (Ulva prolifera), Tokushima (Ulva prolifera), and Ehime prefecture (Ulva linza). Apocarotenoids, such as ionones, and their derivatives were prominent volatiles in algae from Okayama (Ulva prolifera) and Tokushima prefecture (Ulva prolifera). Volatile, short chained apocarotenoids are among the most potent flavor components and contribute to the flavor of fresh, processed algae, and algae-based products. Benzaldehyde was predominant in seaweed from Shizuoka prefecture (Monostroma nitidum). Multivariant statistical analysis (PCA) enabled simple discrimination of the samples based on their volatile profiles. This work shows the potential of SPME-GC-MS coupled with multivariant analysis to discriminate between samples of different geographical and botanical origins and form the basis for development of authentication methods of green algae products, including seasonings. Y1 - 2014 U6 - https://doi.org/10.1155/2014/289780 SN - 1537-744X PB - Hindawi Publishing Corp. CY - New York ER - TY - JOUR A1 - Yadav, Heena A1 - Dreher, Dorothée A1 - Athmer, Benedikt A1 - Porzel, Andrea A1 - Gavrin, Aleksandr A1 - Baldermann, Susanne A1 - Tissier, Alain A1 - Hause, Bettina T1 - Medicago TERPENE SYNTHASE 10 is involved in defense against an oomycete root pathogen JF - Plant physiology : an international journal devoted to physiology, biochemistry, cellular and molecular biology, biophysics and environmental biology of plants N2 - In nature, plants interact with numerous beneficial or pathogenic soil-borne microorganisms. Plants have developed various defense strategies to expel pathogenic microbes, some of which function soon after pathogen infection. We used Medicago truncatula and its oomycete pathogen Aphanomyces euteiches to elucidate early responses of the infected root. A. euteiches causes root rot disease in legumes and is a limiting factor in legume production. Transcript profiling of seedlings and adult plant roots inoculated with A. euteiches zoospores for 2 h revealed specific upregulation of a gene encoding a putative sesquiterpene synthase (M. truncatula TERPENE SYNTHASE 10 [MtTPS10]) in both developmental stages. MtTPS10 was specifically expressed in roots upon oomycete infection. Heterologous expression of MtTPS10 in yeast led to production of a blend of sesquiterpenes and sesquiterpene alcohols, with NMR identifying a major peak corresponding to himalachol. Moreover, plants carrying a tobacco (Nicotiana tabacum) retrotransposon Tnt1 insertion in MtTPS10 lacked the emission of sesquiterpenes upon A. euteiches infection, supporting the assumption that the identified gene encodes a multiproduct sesquiterpene synthase. Mttps10 plants and plants with reduced MtTPS10 transcript levels created by expression of an MtTPS10-artificial microRNA in roots were more susceptible to A. euteiches infection than were the corresponding wild-type plants and roots transformed with the empty vector, respectively. Sesquiterpenes produced by expression of MtTPS10 in yeast also inhibited mycelial growth and A. euteiches zoospore germination. These data suggest that sesquiterpene production in roots by MtTPS10 plays a previously unrecognized role in the defense response of M. truncatula against A. euteiches. Y1 - 2019 U6 - https://doi.org/10.1104/pp.19.00278 SN - 0032-0889 SN - 1532-2548 VL - 180 IS - 3 SP - 1598 EP - 1613 PB - American Society of Plant Physiologists CY - Rockville ER - TY - JOUR A1 - Xu, Mei A1 - Lu, Yong-Ping A1 - Hasan, Ahmed A. A1 - Hocher, Berthold T1 - Plasma ET-1 concentrations are elevated in patients with hypertension meta-analysis of clinical studies JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie ; official organ of the Deutsche Liga zur Bekämpfung des Hohen Blutdruckes e.V., Deutsche Hypertonie-Gesellschaft N2 - Background/Aims: A recent study revealed that global overexpression of ET-1 causes a slight reduction in systemic blood pressure. Moreover, heterozygous ET-1 knockout mice are hypertensive. The role of ET-1 in human hypertension was so far not addressed by a strict meta-analysis of published human clinical studies. Methods: We included studies published between January 1, 1990 and February 28, 2017. We included case control studies analyzing untreated essential hypertension or hypertensive patients where antihypertensive medication was discontinued for at least two weeks. Based on the principle of Cochrane systematic reviews, case control studies (CCSs) in PubMed (Medline) and Google Scholar designed to identify the role of endothelin-1 (ET-1) in the pathophysiological of hypertension were screened. Review Manager Version 5.0 (Rev-Man 5.0) was applied for statistical analysis. Mean difference and 95% confidence interval (CI) were shown in inverse variance (IV) fixed-effects model or IV random-effects models. Results: Eleven studies fulfilling our in-and exclusion criteria were eligible for this meta-analysis. These studies included 450 hypertensive patients and 328 controls. Our meta-analysis revealed that ET-1 plasma concentrations were higher in hypertensive patients as compared to the control patients [mean difference between groups 1.57 pg/mL, 95%Ci [0.47 similar to 2.68, P = 0.005]. These finding were driven by patients having systolic blood pressure higher than 160 mmHg and diastolic blood pressure higher than 100 mmHg. Conclusions: This meta-analysis showed that hypertensive patients do have elevated plasma ET-1 concentrations. This finding is driven by those patients with high systolic/diastolic blood pressure. Given that the ET-1 gene did not appear in any of the whole genome association studies searching for hypertension associated gene loci, it is very likely that the elevated plasma ET-1 concentrations in hypertensive patients are secondary to hypertension and may reflect endothelial cell damage. KW - Hypertension KW - ET-1 KW - Meta-analysis Y1 - 2017 U6 - https://doi.org/10.1159/000477572 SN - 1420-4096 SN - 1423-0143 VL - 42 IS - 2 SP - 304 EP - 313 PB - Karger CY - Basel ER - TY - JOUR A1 - Xiong, Chan A1 - Stiboller, Michael A1 - Glabonjat, Ronald A. A1 - Rieger, Jaqueline A1 - Paton, Lhiam A1 - Francesconi, Kevin A. T1 - Transport of arsenolipids to the milk of a nursing mother after consuming salmon fish JF - Journal of trace elements in medicine and biology N2 - Objective: We address two questions relevant to infants' exposure to potentially toxic arsenolipids, namely, are the arsenolipids naturally present in fish transported intact to a mother's milk, and what is the efficiency of this transport. Methods: We investigated the transport of arsenolipids and other arsenic species present in fish to mother's milk by analyzing the milk of a single nursing mother at 15 sampling times over a 3-day period after she had consumed a meal of salmon. Total arsenic values were obtained by elemental mass spectrometry, and arsenic species were measured by HPLC coupled to both elemental and molecular mass spectrometry. Results: Total arsenic increased from background levels (0.1 mu g As kg(-1)) to a peak value of 1.72 lig As kg(-1) eight hours after the fish meal. The pattern for arsenolipids was similar to that of total arsenic, increasing from undetectable background levels (< 0.01 mu g As kg(-1)) to a peak after eight hours of 0.45 mu g As kg(-1). Most of the remaining total arsenic in the milk was accounted for by arsenobetaine. The major arsenolipids in the salmon were arsenic hydrocarbons (AsHCs; 55 % of total arsenolipids), and these compounds were also the dominant arsenolipids in the milk where they contributed over 90 % of the total arsenolipids. Conclusions: Our study has shown that ca 2-3 % of arsenic hydrocarbons, natural constituents of fish, can be directly transferred unchanged to the milk of a nursing mother. In view of the potential neurotoxicity of AsHCs, the effects of these compounds on the brain developmental stage of infants need to be investigated. KW - human milk KW - arsenolipids KW - salmon fish KW - HPLC/ICPMS KW - HPLC/HR-ESMS Y1 - 2020 U6 - https://doi.org/10.1016/j.jtemb.2020.126502 SN - 0946-672X VL - 61 PB - Elsevier CY - München ER - TY - JOUR A1 - Wright, Stephanie L. A1 - Ulke, Jannis A1 - Font, Anna A1 - Chan, Ka Lung Andrew A1 - Kelly, Frank J. T1 - Atmospheric microplastic deposition in an urban environment and an evaluation of transport JF - Environment international N2 - Microplastics are a global environmental issue contaminating aquatic and terrestrial environments. They have been reported in atmospheric deposition, and indoor and outdoor air, raising concern for public health due to the potential for exposure. Moreover, the atmosphere presents a new vehicle for microplastics to enter the wider environment, yet our knowledge of the quantities, characteristics and pathways of airborne microplastics is sparse. Here we show microplastics in atmospheric deposition in a major population centre, central London. Microplastics were found in all samples, with deposition rates ranging from 575 to 1008 microplastics/m(2)/d. They were found in various shapes, of which fibrous microplastics accounted for the great majority (92%). Across all samples, 15 different petrochemical-based polymers were identified. Bivariate polar plots indicated dependency on wind, with different source areas for fibrous and non-fibrous airborne microplastics. This is the first evidence of airborne microplastics in London and confirms the need to include airborne pathways when consolidating microplastic impacts on the wider environment and human health. KW - microplastics KW - atmospheric deposition KW - air pollution KW - urban Y1 - 2020 U6 - https://doi.org/10.1016/j.envint.2019.105411 SN - 0160-4120 SN - 1873-6750 VL - 136 PB - Elsevier, Pergamon Press CY - New York, NY [u.a.] ER - TY - GEN A1 - Woting, Anni A1 - Blaut, Michael T1 - The intestinal microbiota in metabolic disease T2 - Nutrients N2 - Gut bacteria exert beneficial and harmful effects in metabolic diseases as deduced from the comparison of germfree and conventional mice and from fecal transplantation studies. Compositional microbial changes in diseased subjects have been linked to adiposity, type 2 diabetes and dyslipidemia. Promotion of an increased expression of intestinal nutrient transporters or a modified lipid and bile acid metabolism by the intestinal microbiota could result in an increased nutrient absorption by the host. The degradation of dietary fiber and the subsequent fermentation of monosaccharides to short-chain fatty acids (SCFA) is one of the most controversially discussed mechanisms of how gut bacteria impact host physiology. Fibers reduce the energy density of the diet, and the resulting SCFA promote intestinal gluconeogenesis, incretin formation and subsequently satiety. However, SCFA also deliver energy to the host and support liponeogenesis. Thus far, there is little knowledge on bacterial species that promote or prevent metabolic disease. Clostridium ramosum and Enterococcus cloacae were demonstrated to promote obesity in gnotobiotic mouse models, whereas bifidobacteria and Akkermansia muciniphila were associated with favorable phenotypes in conventional mice, especially when oligofructose was fed. How diet modulates the gut microbiota towards a beneficial or harmful composition needs further research. Gnotobiotic animals are a valuable tool to elucidate mechanisms underlying diet-host-microbe interactions. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 448 KW - intestinal microbiota KW - obesity KW - diabetes KW - metabolic syndrome KW - energy harvest KW - diet KW - absorption KW - bile acids KW - low-grade inflammation KW - SCFA Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-407687 ER - TY - THES A1 - Wolf, Kristine T1 - Produktentwicklung eines luteinhaltigen, kolloidalen Nahrungsergänzungsmittels: physikochemische und ernährungsphysiologische Aspekte N2 - Sekundäre Pflanzenstoffe und ihre gesundheitsfördernden Eigenschaften sind in den letzten zwei Jahrzehnten vielfach ernährungsphysiologisch untersucht und spezifische positive Effekte im humanen Organismus zum Teil sehr genau beschrieben worden. Zu den Carotinoiden zählend ist der sekundäre Pflanzenstoff Lutein insbesondere in der Prävention von ophthalmologischen Erkrankungen in den Mittelpunkt der Forschung gerückt. Das ausschließlich von Pflanzen und einigen Algen synthetisierte Xanthophyll wird über die pflanzliche Nahrung insbesondere grünes Blattgemüse in den humanen Organismus aufgenommen. Dort akkumuliert es bevorzugt im Makulapigment der Retina des menschlichen Auges und ist bedeutend im Prozess der Aufrechterhaltung der Funktionsfähigkeit der Photorezeptorzellen. Im Laufe des Alterns kann die Abnahme der Dichte des Makulapigments und der Abbau von Lutein beobachtet werden. Die dadurch eintretende Destabilisierung der Photorezeptorzellen im Zusammenhang mit einer veränderten Stoffwechsellage im alternden Organismus kann zur Ausprägung der altersbedingten Makuladegeneration (AMD) führen. Die pathologische Symptomatik der Augenerkrankung reicht vom Verlust der Sehschärfe bis hin zum irreversiblen Erblinden. Da therapeutische Mittel ausschließlich ein Fortschreiten verhindern, bestehen hier Forschungsansätze präventive Maßnahmen zu finden. Die Supplementierung von luteinhaltigen Präparaten bietet dabei einen Ansatzpunkt. Auf dem Markt finden sich bereits Nahrungsergänzungsmittel (NEM) mit Lutein in verschiedenen Applikationen. Limitierend ist dabei die Stabilität und Bioverfügbarkeit von Lutein, welches teilweise kostenintensiv und mit unbekannter Reinheit zu erwerben ist. Aus diesem Grund wäre die Verwendung von Luteinestern als die pflanzliche Speicherform des Luteins im Rahmen eines NEMs vorteilhaft. Neben ihrer natürlichen, höheren Stabilität sind Luteinester nachhaltig und kostengünstig einsetzbar. In dieser Arbeit wurden physikochemische und ernährungsphysiologisch relevante Aspekte in dem Produktentwicklungsprozess eines NEMs mit Luteinestern in einer kolloidalen Formulierung untersucht. Die bisher einzigartige Anwendung von Luteinestern in einem Mundspray sollte die Aufnahme des Wirkstoffes insbesondere für ältere Menschen erleichtern und verbessern. Unter Beachtung der Ergebnisse und der ernährungsphysiologischen Bewertung sollten u.a. Empfehlungen für die Rezepturzusammensetzungen einer Miniemulsion (Emulsion mit Partikelgrößen <1,0 µm) gegeben werden. Eine Einschätzung der Bioverfügbarkeit der Luteinester aus den entwickelten, kolloidalen Formulierungen konnte anhand von Studien zur Resorption- und Absorptionsverfügbarkeit in vitro ermöglicht werden. In physikalischen Untersuchungen wurden zunächst Basisbestandteile für die Formulierungen präzisiert. In ersten wirkstofffreien Musteremulsionen konnten ausgewählte Öle als Trägerphase sowie Emulgatoren und Löslichkeitsvermittler (Peptisatoren) hinsichtlich ihrer Eignung zur Bereitstellung einer Miniemulsion physikalisch geprüft werden. Die beste Stabilität und optimale Eigenschaften einer Miniemulsion zeigten sich bei der Verwendung von MCT-Öl (engl. medium chain triglyceride) bzw. Rapsöl in der Trägerphase sowie des Emulgators Tween® 80 (Tween 80) allein oder in Kombination mit dem Molkenproteinhydrolysat Biozate® 1 (Biozate 1). Aus den physikalischen Untersuchungen der Musteremulsionen gingen die Präemulsionen als Prototypen hervor. Diese enthielten den Wirkstoff Lutein in verschiedenen Formen. So wurden Präemulsionen mit Lutein, mit Luteinestern sowie mit Lutein und Luteinestern konzipiert, welche den Emulgator Tween 80 oder die Kombination mit Biozate 1 enthielten. Bei der Herstellung der Präemulsionen führte die Anwendung der Emulgiertechniken Ultraschall mit anschließender Hochdruckhomogenisation zu den gewünschten Miniemulsionen. Beide eingesetzten Emulgatoren boten optimale Stabilisierungseffekte. Anschließend erfolgte die physikochemische Charakterisierung der Wirkstoffe. Insbesondere Luteinester aus Oleoresin erwiesen sich hier als stabil gegenüber verschiedenen Lagerungsbedingungen. Ebenso konnte bei einer kurzzeitigen Behandlung der Wirkstoffe unter spezifischen mechanischen, thermischen, sauren und basischen Bedingungen eine Stabilität von Lutein und Luteinestern gezeigt werden. Die Zugabe von Biozate 1 bot dabei nur für Lutein einen zusätzlichen Schutz. Bei längerer physikochemischer Behandlung unterlagen die in den Miniemulsionen eingebrachten Wirkstoffe moderaten Abbauvorgängen. Markant war deren Sensitivität gegenüber dem basischen Milieu. Im Rahmen der Rezepturentwicklung des NEMs war hier die Empfehlung, eine Miniemulsion mit einem leicht saurem pH-Milieu zum Schutz des Wirkstoffes durch kontrollierte Zugabe weiterer Inhaltstoffe zu gestalten. Im weiteren Entwicklungsprozess des NEMs wurden Fertigrezepturen mit dem Wirkstoff Luteinester aufgestellt. Die alleinige Anwendung des Emulgators Biozate 1 zeigte sich dabei als ungeeignet. Die weiterhin zur Verfügung stehenden Fertigrezepturen enthielten in der Öl-phase neben dem Wirkstoff das MCT-ÖL oder Rapsöl sowie a-Tocopherol zur Stabilisierung. Die Wasserphase bestand aus dem Emulgator Tween 80 oder einer Kombination aus Tween 80 und Biozate 1. Zusatzstoffe waren zudem als mikrobiologischer Schutz Ascorbinsäure und Kaliumsorbat sowie für sensorische Effekte Xylitol und Orangenaroma. Die Anordnung der Basisrezeptur und das angewendete Emulgierverfahren lieferten stabile Miniemulsionen. Weiterhin zeigten langfristige Lagerungsversuche mit den Fertigrezepturen bei 4°C, dass eine Aufrechterhaltung der geforderten Luteinestermenge im Produkt gewährleistet war. Analoge Untersuchungen an einem luteinhaltigen, marktgängigen Präparat bestätigten dagegen eine bereits bei kurzfristiger Lagerung auftretende Instabilität von Lutein. Abschließend wurde durch Resorptions- und Absorptionsstudien in vitro mit den Präemulsionen und Fertigrezepturen die Bioverfügbarkeit von Luteinestern geprüft. Nach Behandlung in einem etablierten in vitro Verdaumodell konnte eine geringfügige Resorptionsverfügbarkeit der Luteinester definiert werden. Limitiert war eine Micellarisierung des Wirkstoffes aus den konzipierten Formulierungen zu beobachten. Eine enzymatische Spaltung der Luteinester zu freiem Lutein wurde nur begrenzt festgestellt. Spezifität und Aktivität von entsprechenden hydrolytischen Lipasen sind als äußerst gering gegenüber Luteinestern zu bewerten. In sich anschließenden Zellkulturversuchen mit der Zelllinie Caco-2 wurden keine zytotoxischen Effekte durch die relevanten Inhaltsstoffe in den Präemulsionen gezeigt. Dagegen konnten eine Sensibilität gegenüber den Fertigrezepturen beobachtet werden. Diese sollte im Zusammenhang mit Irritationen der Schleimhäute des Magen-Darm-Traktes bedacht werden. Eine weniger komplexe Rezeptur könnte die beobachteten Einschränkungen möglicherweise minimieren. Abschließende Absorptionsstudien zeigten, dass grundsätzlich eine geringfügige Aufnahme von vorrangig Lutein, aber auch Luteinmonoestern in den Enterocyten aus Miniemulsionen erfolgen kann. Dabei hatte weder Tween 80 noch Biozate 1 einen förderlichen Einfluss auf die Absorptionsrate von Lutein oder Luteinestern. Die Metabolisierung der Wirkstoffe durch vorherigen in vitro-Verdau steigerte die zelluläre Aufnahme von Wirkstoffen aus Formulierungen mit Lutein und Luteinestern gleichermaßen. Die beobachtete Aufnahme von Lutein und Luteinmonoestern in den Enterocyten scheint über passive Diffusion zu erfolgen, wobei auch der aktive Transport nicht ausgeschlossen werden kann. Dagegen können Luteindiester aufgrund ihrer Molekülgröße nicht über den Weg der Micellarisierung und einfachen Diffusion in die Enterocyten gelangen. Ihre Aufnahme in die Dünndarmepithelzellen bedarf einer vorherigen hydrolytischen Spaltung durch spezifische Lipasen. Dieser Schritt limitiert wiederum die effektive Aufnahme der Luteinester in die Zellen bzw. stellt eine Einschränkung in ihrer Bioverfügbarkeit im Vergleich zu freiem Lutein dar. Zusammenfassend konnte für die physikochemisch stabilen Luteinester eine geringe Bioverfügbarkeit aus kolloidalen Formulierungen gezeigt werden. Dennoch ist die Verwendung als Wirkstoffquelle für den sekundären Pflanzenstoff Lutein in einem NEM zu empfehlen. Im Zusammenhang mit der Aufnahme von luteinreichen, pflanzlichen Lebensmitteln kann trotz der zu erwartenden geringen Bioverfügbarkeit der Luteinester aus dem NEM ein Beitrag zur Verbesserung des Luteinstatus erreicht werden. Entsprechende Publikationen zeigten eindeutige Korrelationen zwischen der Aufnahme von luteinesterhaltigen Präparaten und einem Anstieg der Luteinkonzentration im Serum bzw. der Makulapigmentdichte in vivo. Die geringfügig bessere Bioverfügbarkeit von freiem Lutein steht im kritischen Zusammenhang mit seiner Instabilität und Kostenintensität. Bilanzierend wurde im Rahmen dieser Arbeit das marktgängige Produkt Vita Culus® konzipiert. Im Ausblick sollten humane Interventionsstudien mit dem NEM die abschließende Bewertung der Bioverfügbarkeit von Luteinestern aus dem Präparat möglich machen. N2 - Secondary plant metabolites and their health-promoting properties have been studied and pub-lished over the past two decades. Their specificity with regard to positive properties and effects in the human organism has been described precisely. Among the carotenoids, the secondary plant metabolite lutein has become the focus of research, particularly in the prevention of ophthalmic diseases. The xanthophyll, which is synthesized exclusively by plants (incl. some algae), is absorbed into the human organism through plant food especially green leafy vegetables. There it accumulates preferentially in the macular pigment of the retina of the human eye and is important in the process of maintaining the functionality of the photoreceptors. As the aging progresses, the decrease in the density of the macular pigment and the depletion of lutein can be observed. The resulting destabilization of the photoreceptors in connection with a changed metabolism in the aging organism can lead to the development of age-related macular degeneration (AMD). The pathological symptoms of AMD range from loss of visual acuity to irreversible blindness. Since therapeutic agents only enable the disease to be decelerated or come to a standstill, research approaches exist to find preventive measures. The supplementation of preparations containing lutein offers a starting point to have a targeted positive effect on the stability of the macular pigment density and thus to maintain the quality of vision even in old age. Dietary supplements (DS) with lutein in various applications are available on the market. Limiting is the stability and bioavailability of lutein, which can be expensive and acquired with unknown purity. For this reason, the use of the storage form of lutein in plants, the lutein esters within the framework of a DS would be advantageous. In addition to their natural, higher stability, lutein esters can be used sustainably and inexpensively. In this thesis, physicochemical and nutritionally relevant aspects in the product development process of a DS with lutein esters in a colloidal formulation were investigated. The hitherto unique use of lutein esters in oral spray applications should facilitate and improve the absorption of the active ingredient especially for older people. Taking into account the results and the nutritional assessment, recommendations for the recipe compositions of a miniemulsions (emulsion with particle sizes <1.0 µm) are given. An assessment of the bioavailability of the lutein esters from the developed colloidal formulations was realized by means of studies on the absorption accessibility and availability in vitro. In physical investigations, the basic components for the colloidal formulations to be developed were first specified. In the first active ingredient-free sample emulsions selected oils as carrier phase as well as emulsifiers and solubilizers (peptizers) could be physically tested with regard to their suitability for providing a miniemulsion. The best stability and optimal properties of a miniemulsion were found when using MCT oil (medium chain triglyceride) or rapeseed oil in the carrier phase and the emulsifier Tween® 80 (Tween 80) alone or in combination with the whey protein hydrolyzate Biozate® 1 (Biozate 1) in the aqueous phase. The pre-emulsions were developed as prototypes from the physical examinations of the basic recipes. These contained the active ingredient lutein in various forms. Pre-emulsions with lutein, with lutein esters or with lutein and lutein esters were prepared. They contained the emulsifier Tween 80 or the combination with Biozate 1. In the preparation of the pre-emulsions the use of ultrasound emulsification techniques with subsequent high-pressure homogenization led to the postulated miniemulsions. Both emulsifiers used offered optimal stabilization effects. This was followed by the physicochemical characterization of the active substances in the pre-emulsions. In particular, lutein esters from oleoresin were found to be stable against various storage conditions. A short-term treatment of the active ingredients under specific mechanical, thermal, acidic and basic conditions also demonstrated the stability of lutein and lutein esters. The addition of Biozate 1 offered further protection for lutein. In the case of prolonged physico-chemical treatment, the active substances incorporated in the miniemulsions were subject to moderate degradation processes. The sensitivity of the active ingredients in the formulations to a basic environment was striking. As part of the formulation development of the DS, the recommendation was given to design a miniemulsion with a slightly acidic environment by the controlled addition of further ingredients to protect the active ingredient. In the further development process of the DS, refined formulations with the active ingredient lutein ester and modifications of the emulsifiers were then set up. The sole use of the emulsifier Biozate 1 turned out to be unsuitable and these formulations were rejected. The refined formulations that were still available contained the carriers MCT oil or rapeseed oil as well as a-tocopherol for stabilization. The water phase consisted of the emulsifier Tween 80 or a combination of Tween 80 and Biozate 1. Additives were ascorbic acid and potassium sorbate for microbial protection such as xylitol and orange aroma for sensory effects. The arrangement of the basic recipe and the emulsifying process used provided stable miniemulsions. Long-term storage tests with the ready formulations at 4°C showed that the required amount of lutein ester is maintained in the product. Analogous tests on a preparation containing lutein confirmed the instability of lutein, which occurs even in the case of short-term storage. Finally, the bioavailability of the lutein esters was investigated using the pre-emulsions and refined formulations in studies of absorption accessibility and availability in vitro. For these studies an in vitro digestion model was confirmed. After treatment of the formulations in this model a slight absorption accessibility of the lutein esters could be classified. Micellarization process and enzymatic cleavage of the lutein esters to free lutein has only been found to a limited extent. The specificity and activity of corresponding hydrolytic lipases to lutein esters can be rated as extremely low. In subsequent cell culture experiments with the Caco-2 cell line, no cytotoxic effects were shown by the relevant ingredients in the pre-emulsions. In contrast, sensitivity to the refined formulations could be observed. This should be considered in connection with irritation of the mucous membranes of the gastrointestinal tract. A less complex formulation could possibly prevent the observed restrictions. In studies of absorption availability in vitro a low uptake of primarily free lutein, but also lutein monoesters in the enterocytes from miniemulsions could be observed. Neither Tween 80 nor Biozate 1 have a beneficial influence on the absorption rate of lutein or lutein esters. But micellarization of the active ingredients through previous in vitro digestion increased the cellular uptake of lutein and lutein esters from the formulations. This gives an evidence of the relevance of micellarization in absorption of lipophilic substances. The uptake of lutein and lutein monoesters in the enterocytes seems to be possible via passive diffusion, although active transport cannot be ruled out either. On the other hand, due to their molecular size, lutein diesters cannot enter into the enterocytes via micellarization or simple diffusion. Their absorption in the small intestine epithelial cells requires prior hydrolytic cleavage by specific lipases. This step in turn limits the effective absorption of the lutein esters into the cells or represents a restriction in their bioavailability in comparison to free lutein. In summary, a low bioavailability for the physicochemically stable lutein esters from colloidal formulations was shown. Nevertheless, the use as a source of active ingredients for the xanthophyll lutein in a DS is recommended. In connection with the intake of plant foods rich in lutein, a contribution to improving the lutein status can be achieved despite the expected low bioavailability of the lutein esters from the DS. Corresponding publications showed clear correlations between the intake of preparations containing lutein ester and an increase in serum lutein concentrations or the macular pigment density in vivo. The slightly better bioavailability of free lutein is critically linked to its instability and cost intensity. On the basis of this work, the product Vita Culus® was designed and is available on the market. As a prospect of future research, human intervention studies with the DS should be conducted to assess the total bio-availability of lutein esters from miniemulsions in detail. T2 - Product development of a lutein-containing, colloidal dietary supplement: physicochemical and nutritional aspects KW - Luteinester KW - Emulsion KW - Nahrunsgergänzungsmittel KW - Bioverfügbarkeit KW - lutein esters KW - emulsion KW - dietary supplements KW - bioavailability Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-487743 ER - TY - THES A1 - Wohlgemuth, Steffen T1 - Microbial and host factors associated with chronic intestinal inflammation of the Interleukin-10 deficient mouse Y1 - 2010 CY - Potsdam ER - TY - JOUR A1 - Witzel, Katja A1 - Strehmel, Nadine A1 - Baldermann, Susanne A1 - Neugart, Susanne A1 - Becker, Yvonne A1 - Becker, Matthias A1 - Berger, Beatrice A1 - Scheel, Dierk A1 - Grosch, Rita A1 - Schreiner, Monika A1 - Ruppel, Silke T1 - Arabidopsis thaliana root and root exudate metabolism is altered by the growth-promoting bacterium Kosakonia radicincitans DSM 16656(T) JF - Plant and soil N2 - Plant growth-promoting bacteria (PGPB) affect host physiological processes in various ways. This study aims at elucidating the dependence of bacterial-induced growth promotion on the plant genotype and characterizing plant metabolic adaptations to PGPB. Eighteen Arabidopsis thaliana accessions were inoculated with the PGPB strain Kosakonia radicincitans DSM 16656(T). Colonisation pattern was assessed by enhanced green fluorescent protein (eGFP)-tagged K. radicincitans in three A. thaliana accessions differing in their growth response. Metabolic impact of bacterial colonisation was determined for the best responding accession by profiling distinct classes of plant secondary metabolites and root exudates. Inoculation of 18 A. thaliana accessions resulted in a wide range of growth responses, from repression to enhancement. Testing the bacterial colonisation of three accessions did not reveal a differential pattern. Profiling of plant secondary metabolites showed a differential accumulation of glucosinolates, phenylpropanoids and carotenoids in roots. Analysis of root exudates demonstrated that primary and secondary metabolites were predominantly differentially depleted by bacterial inoculation. The plant genotype controls the bacterial growth promoting traits. Levels of lutein and beta-carotene were elevated in inoculated roots. Supplementing a bacterial suspension with beta-carotene increased bacterial growth, while this was not the case when lutein was applied, indicating that beta-carotene could be a positive regulator of plant growth promotion. KW - Arabidopsis KW - Carotenoids KW - Glucosinolates KW - Plant growth promoting bacteria KW - Phenylpropanoids KW - Root exudates Y1 - 2017 U6 - https://doi.org/10.1007/s11104-017-3371-1 SN - 0032-079X SN - 1573-5036 VL - 419 SP - 557 EP - 573 PB - Springer CY - Dordrecht ER - TY - JOUR A1 - Witzel, Katja A1 - Neugart, Susanne A1 - Ruppel, Silke A1 - Schreiner, Monika A1 - Wiesner, Melanie A1 - Baldermann, Susanne T1 - Recent progress in the use of 'omics technologies in brassicaceous vegetables JF - Frontiers in plant science N2 - Continuing advances in 'omics methodologies and instrumentation is enhancing the understanding of how plants cope with the dynamic nature of their growing environment. 'Omics platforms have been only recently extended to cover horticultural crop species. Many of the most widely cultivated vegetable crops belong to the genus Brassica: these include plants grown for their root (turnip, rutabaga/swede), their swollen stem base (kohlrabi), their leaves (cabbage, kale, pak choi) and their inflorescence (cauliflower, broccoli). Characterization at the genome, transcript, protein and metabolite levels has illustrated the complexity of the cellular response to a whole series of environmental stresses, including nutrient deficiency, pathogen attack, heavy metal toxicity, cold acclimation, and excessive and sub optimal irradiation. This review covers recent applications of omics technologies to the brassicaceous vegetables, and discusses future scenarios in achieving improvements in crop end-use quality. KW - genomics KW - transcriptomics KW - metabolomics KW - proteomics KW - crop KW - microbiomics Y1 - 2015 U6 - https://doi.org/10.3389/fpls.2015.00244 SN - 1664-462X VL - 6 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Wittenbecher, Clemens A1 - Ouni, Meriem A1 - Kuxhaus, Olga A1 - Jähnert, Markus A1 - Gottmann, Pascal A1 - Teichmann, Andrea A1 - Meidtner, Karina A1 - Kriebel, Jennifer A1 - Grallert, Harald A1 - Pischon, Tobias A1 - Boeing, Heiner A1 - Schulze, Matthias Bernd A1 - Schürmann, Annette T1 - Insulin-Like Growth Factor Binding Protein 2 (IGFBP-2) and the Risk of Developing Type 2 Diabetes JF - Diabetes : a journal of the American Diabetes Association N2 - Recent studies suggest that insulin-like growth factor binding protein 2 (IGFBP-2) may protect against type 2 diabetes, but population-based human studies are scarce. We aimed to investigate the prospective association of circulating IGFBP-2 concentrations and of differential methylation in the IGFBP-2 gene with type 2 diabetes risk. Y1 - 2019 U6 - https://doi.org/10.2337/db18-0620 SN - 0012-1797 SN - 1939-327X VL - 68 IS - 1 SP - 188 EP - 197 PB - American Diabetes Association CY - Alexandria ER - TY - JOUR A1 - Wittenbecher, Clemens A1 - Kuxhaus, Olga A1 - Boeing, Heiner A1 - Stefan, Norbert A1 - Schulze, Matthias Bernd T1 - Associations of short stature and components of height with incidence of type 2 diabetes BT - mediating effects of cardiometabolic risk factors JF - Diabetologia : journal of the European Association for the Study of Diabetes (EASD) N2 - Aims/hypothesis This study aimed to evaluate associations of height as well as components of height (sitting height and leg length) with risk of type 2 diabetes and to explore to what extent associations are explainable by liver fat and cardiometabolic risk markers. Methods A case-cohort study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study comprising 26,437 participants who provided blood samples was designed. We randomly selected a subcohort of 2500 individuals (2029 diabetes-free at baseline and with anamnestic, anthropometrical and metabolic data for analysis). Of the 820 incident diabetes cases identified in the full cohort during 7 years of follow-up, 698 remained for analyses after similar exclusions. Results After adjustment for age, potential lifestyle confounders, education and waist circumference, greater height was related to lower diabetes risk (HR per 10 cm, men 0.59 [95% CI 0.47, 0.75] and women 0.67 [0.51, 0.88], respectively). Leg length was related to lower risk among men and women, but only among men if adjusted for total height. Adjustment for liver fat and triacylglycerols, adiponectin and C-reactive protein substantially attenuated associations between height and diabetes risk, particularly among women. Conclusions/interpretation We observed inverse associations between height and risk of type 2 diabetes, which was largely related to leg length among men. The inverse associations may be partly driven by lower liver fat content and a more favourable cardiometabolic profile. KW - Adult height KW - Blood pressure KW - Diabetes incidence KW - Leg length KW - Liver fat KW - Short stature KW - Trunk length Y1 - 2019 U6 - https://doi.org/10.1007/s00125-019-04978-8 SN - 0012-186X SN - 1432-0428 VL - 62 IS - 12 SP - 2211 EP - 2221 PB - Springer CY - New York ER - TY - THES A1 - Wittenbecher, Clemens T1 - Linking whole-grain bread, coffee, and red meat to the risk of type 2 diabetes T1 - Der Einfluss von Vollkornbrot, Kaffee, und rotem Fleisch auf das Typ 2 Diabetesrisiko BT - using metabolomics networks to infer potential biological mechanisms BT - Verwendung von Metabolomics-Netzwerken, um auf biologische Mechanismen zu schließen N2 - Background: Consumption of whole-grain, coffee, and red meat were consistently related to the risk of developing type 2 diabetes in prospective cohort studies, but potentially underlying biological mechanisms are not well understood. Metabolomics profiles were shown to be sensitive to these dietary exposures, and at the same time to be informative with respect to the risk of type 2 diabetes. Moreover, graphical network-models were demonstrated to reflect the biological processes underlying high-dimensional metabolomics profiles. Aim: The aim of this study was to infer hypotheses on the biological mechanisms that link consumption of whole-grain bread, coffee, and red meat, respectively, to the risk of developing type 2 diabetes. More specifically, it was aimed to consider network models of amino acid and lipid profiles as potential mediators of these risk-relations. Study population: Analyses were conducted in the prospective EPIC-Potsdam cohort (n = 27,548), applying a nested case-cohort design (n = 2731, including 692 incident diabetes cases). Habitual diet was assessed with validated semiquantitative food-frequency questionnaires. Concentrations of 126 metabolites (acylcarnitines, phosphatidylcholines, sphingomyelins, amino acids) were determined in baseline-serum samples. Incident type 2 diabetes cases were assed and validated in an active follow-up procedure. The median follow-up time was 6.6 years. Analytical design: The methodological approach was conceptually based on counterfactual causal inference theory. Observations on the network-encoded conditional independence structure restricted the space of possible causal explanations of observed metabolomics-data patterns. Given basic directionality assumptions (diet affects metabolism; metabolism affects future diabetes incidence), adjustment for a subset of direct neighbours was sufficient to consistently estimate network-independent direct effects. Further model-specification, however, was limited due to missing directionality information on the links between metabolites. Therefore, a multi-model approach was applied to infer the bounds of possible direct effects. All metabolite-exposure links and metabolite-outcome links, respectively, were classified into one of three categories: direct effect, ambiguous (some models indicated an effect others not), and no-effect. Cross-sectional and longitudinal relations were evaluated in multivariable-adjusted linear regression and Cox proportional hazard regression models, respectively. Models were comprehensively adjusted for age, sex, body mass index, prevalence of hypertension, dietary and lifestyle factors, and medication. Results: Consumption of whole-grain bread was related to lower levels of several lipid metabolites with saturated and monounsaturated fatty acids. Coffee was related to lower aromatic and branched-chain amino acids, and had potential effects on the fatty acid profile within lipid classes. Red meat was linked to lower glycine levels and was related to higher circulating concentrations of branched-chain amino acids. In addition, potential marked effects of red meat consumption on the fatty acid composition within the investigated lipid classes were identified. Moreover, potential beneficial and adverse direct effects of metabolites on type 2 diabetes risk were detected. Aromatic amino acids and lipid metabolites with even-chain saturated (C14-C18) and with specific polyunsaturated fatty acids had adverse effects on type 2 diabetes risk. Glycine, glutamine, and lipid metabolites with monounsaturated fatty acids and with other species of polyunsaturated fatty acids were classified as having direct beneficial effects on type 2 diabetes risk. Potential mediators of the diet-diabetes links were identified by graphically overlaying this information in network models. Mediation analyses revealed that effects on lipid metabolites could potentially explain about one fourth of the whole-grain bread effect on type 2 diabetes risk; and that effects of coffee and red meat consumption on amino acid and lipid profiles could potentially explain about two thirds of the altered type 2 diabetes risk linked to these dietary exposures. Conclusion: An algorithm was developed that is capable to integrate single external variables (continuous exposures, survival time) and high-dimensional metabolomics-data in a joint graphical model. Application to the EPIC-Potsdam cohort study revealed that the observed conditional independence patterns were consistent with the a priori mediation hypothesis: Early effects on lipid and amino acid metabolism had the potential to explain large parts of the link between three of the most widely discussed diabetes-related dietary exposures and the risk of developing type 2 diabetes. N2 - Hintergrund: Evidenz aus prospektiven Kohortenstudien belegt, dass der gewohnheitsmäßige Verzehr von Vollkorn, Kaffee und rotem Fleisch mit dem Risiko an Typ 2 Diabetes zu erkranken assoziiert ist. Dieser Risikobeziehung eventuell zugrunde liegende Mechanismen sind allerdings noch weitgehend unklar. Des Weiteren wurde gezeigt, dass Metabolitenprofile im Blut durch die oben genannten Ernährungs-expositionen beeinflusst werden und außerdem in Zusammenhang mit dem Typ 2 Diabetesrisiko stehen. Zusätzlich wurde beschrieben, dass grafische Netzwerkmodelle von Metabolitenprofilen die zugrunde liegenden Stoffwechselprozesse gut abbilden. Zielstellung: Das Ziel dieser Arbeit war es, Hypothesen bezüglich biologischer Mechanismen zu generieren, die die Assoziationen des Vollkornverzehrs, des Kaffeekonsums und des Fleischverzehrs mit dem Typ 2 Diabetesrisiko erklären könnten. Im speziellen sollten Aminosäure- und Lipidprofile als mögliche Mediatoren des Risikozusammenhangs untersucht werden. Studienpopulation: Analysen wurden auf Grundlage von Daten aus der prospektiven EPIC-Potsdam Kohortenstudie (n=27,548) durchgeführt, wobei ein Fall-Kohorten-Design verwendet wurde (n=2317, darunter 692 inzidente Typ 2 Diabetesfälle). Ernährungsgewohnheiten wurden mit einem validierten, semiquantitativen Verzehrshäufigkeitsfragebogen erfasst. Die Konzentrationen von 126 Metaboliten (Aminosäuren, Acylcarnitine, Sphingomyeline und Phosphatidylcholine) wurden zur Basiserhebung genommen Blutproben gemessen. Inzidente Typ 2 Diabetesfälle wurden im Rahmen einer aktiven Folgeerhebung detektiert und verifiziert. Die mediane Dauer des berücksichtigten prospektiven Erhebungszeitraums lag für diese Studie bei 6,6 Jahren. Aufbau der Analysen: Die theoretische Grundlage für den methodischen Ansatz dieser Arbeit bildete die kontrafaktische Theorie der Kausalinferenz. Die in Netzwerken kodierte konditionale Unabhängigkeitsstruktur wurde genutzt, um den Raum möglicher Modelle zu begrenzen, die die beobachteten Zusammenhänge zwischen den Metaboliten erklären könnten. Unter Annahme weniger grundlegender Effektrichtungen (von der Ernährung auf die Netzwerke gerichtete Effekte; von den Netzwerken auf das Diabetesrisiko gerichtete Effekte) genügt die Adjustierung für eine Teilmenge der direkten Nachbarn im Netzwerk, um netzwerkunabhängige direkte Effekte konsistent zu schätzen. Eine weitere Spezifizierung der Modelle war allerdings aufgrund fehlender Richtungsinformationen zu den Metaboliten-abhängigkeiten nicht möglich. Deshalb wurde ein Multi-Modellierungsansatz gewählt, um die Grenzen möglicher Effekte zu schlussfolgern. Alle möglichen Ernährungs-Metaboliten-Beziehungen und Metaboliten-Typ 2 Diabetesrisiko-Beziehungen wurden dadurch in eine der folgenden drei Kategorien klassifiziert: Direkter Effekt, Unklar, Kein Effekt. Querschnittsbeziehungen wurden in multivariabel adjustierten linearen Regressionsmodellen untersucht. Longitudinale Zusammenhänge wurden mit Cox-Regressionsmodellen geschätzt. Alle Modelle wurden für Alter, Geschlecht, Body-Mass-Index, prävalente Hypertonie, Ernährungs- und Lebensstilfaktoren und die Einnahme von Medikamenten adjustiert. Ergebnisse: Der Verzehr von Vollkornbrot stand im Zusammenhang mit niedrigeren Konzentrationen gesättigter und einfach ungesättigter Fettsäuren. Kaffee stand in Beziehung zu niedrigeren Konzentrationen verzweigtkettiger und aromatischer Aminosäuren und hatte potentielle Effekte auf das Fettsäureprofil in den Lipidmetaboliten. Rotes Fleisch zeigte einen Zusammenhang mit niedrigeren Glyzinspiegeln und mit höheren Konzentrationen verzweigtkettiger Aminosäuren. Außerdem stand das Fettsäureprofil in den verschieden Gruppen von Lipidmetaboliten in Zusammenhang mit dem Fleischverzehr. Des Weiteren wurden potentielle Effekte der Metabolite auf das Typ 2 Diabetesrisiko gefunden. Aromatische Aminosäuren und Lipidmetabolite mit geradzahligen, gesättigten (C14-C16) und mit spezifischen mehrfach ungesättigten Fettsäureseitenketten standen mit einem erhöhten Typ 2 Diabetesrisiko in Beziehung. Glyzin, Glutamin und Lipidmetabolite mit einfach ungesättigten und anderen mehrfach ungesättigten Fettsäureseitenketten zeigten einen günstigen Zusammenhang mit dem Diabetesrisiko. Mögliche Mediatoren der Beziehung der Ernährungsexpositionen wurden identifiziert, indem diese Informationen in gemeinsamen grafischen Modellen integriert wurden. Mediationsanalysen zeigten, dass die möglichen Effekte von Vollkornverzehr auf die Lipidmetabolite ungefähr ein Viertel des günstigen Einflusses von Vollkornverzehr auf das Diabetesrisikos erklären könnten. Die möglichen Effekte von Kaffeekonsum und von Fleischverzehr auf Aminosäuren und Lipidmetabolite könnten jeweils ungefähr zwei Drittel der Zusammenhänge mit dem Diabetesrisiko erklären. Schlussfolgerung: Grundlage für die Ergebnisse dieser Arbeit war die Entwicklung eines Algorithmus, der externe Faktoren (kontinuierlich Expositionsvariablen, Ereigniszeit-Daten) und hochdimensionale Metabolitenprofile in einem gemeinsamen grafischen Modell integriert. Die Anwendung dieses Algorithmus auf Daten aus der EPIC-Potsdam Kohortenstudie hat gezeigt, dass die beobachteten konditionalen Unabhängigkeitsstrukturen mit der a priori Mediationshypothese konsistent waren. Der frühe Einfluss auf den Aminosäure- und Lipidstoffwechsel könnte die beobachteten Zusammenhänge zwischen drei wichtigen Ernährungsfaktoren und dem Risiko an Typ 2 Diabetes zu erkranken zu großen Teilen erklären. KW - type 2 diabetes KW - nutrition KW - lipid metabolism KW - metabolomics KW - epidemiology KW - networks KW - graphical models KW - mediation analysis KW - red meat KW - whole-grain KW - Diabetes mellitus Typ 2 KW - Ernährung KW - Fettstoffwechsel KW - Metabolomics KW - Epidemiologie KW - Netzwerke KW - grafische Modelle KW - Mediationsanalyse KW - rotes Fleisch KW - Vollkorn KW - Kaffee KW - coffee Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-404592 ER - TY - THES A1 - Wittek, Laura T1 - Comparison of metabolic cages - analysis of refinement measures on the welfare and metabolic parameters of laboratory mice T1 - Der Vergleich von Stoffwechselkäfigen - Analyse von Refinement-Maßnahmen auf das Wohlbefinden und Stoffwechselparameter von Labormäusen N2 - Housing in metabolic cages can induce a pronounced stress response. Metabolic cage systems imply housing mice on metal wire mesh for the collection of urine and feces in addition to monitoring food and water intake. Moreover, mice are single-housed, and no nesting, bedding, or enrichment material is provided, which is often argued to have a not negligible impact on animal welfare due to cold stress. We therefore attempted to reduce stress during metabolic cage housing for mice by comparing an innovative metabolic cage (IMC) with a commercially available metabolic cage from Tecniplast GmbH (TMC) and a control cage. Substantial refinement measures were incorporated into the IMC cage design. In the frame of a multifactorial approach for severity assessment, parameters such as body weight, body composition, food intake, cage and body surface temperature (thermal imaging), mRNA expression of uncoupling protein 1 (Ucp1) in brown adipose tissue (BAT), fur score, and fecal corticosterone metabolites (CMs) were included. Female and male C57BL/6J mice were single-housed for 24 h in either conventional Macrolon cages (control), IMC, or TMC for two sessions. Body weight decreased less in the IMC (females—1st restraint: 6.94%; 2nd restraint: 6.89%; males—1st restraint: 8.08%; 2nd restraint: 5.82%) compared to the TMC (females—1st restraint: 13.2%; 2nd restraint: 15.0%; males—1st restraint: 13.1%; 2nd restraint: 14.9%) and the IMC possessed a higher cage temperature (females—1st restraint: 23.7°C; 2nd restraint: 23.5 °C; males—1st restraint: 23.3 °C; 2nd restraint: 23.5 °C) compared with the TMC (females—1st restraint: 22.4 °C; 2nd restraint: 22.5 °C; males—1st restraint: 22.6 °C; 2nd restraint: 22.4 °C). The concentration of fecal corticosterone metabolites in the TMC (females—1st restraint: 1376 ng/g dry weight (DW); 2nd restraint: 2098 ng/g DW; males—1st restraint: 1030 ng/g DW; 2nd restraint: 1163 ng/g DW) was higher compared to control cage housing (females—1st restraint: 640 ng/g DW; 2nd restraint: 941 ng/g DW; males—1st restraint: 504 ng/g DW; 2nd restraint: 537 ng/g DW). Our results show the stress potential induced by metabolic cage restraint that is markedly influenced by the lower housing temperature. The IMC represents a first attempt to target cold stress reduction during metabolic cage application thereby producing more animal welfare friendly data. N2 - Die Unterbringung in Stoffwechselkäfigen kann eine ausgeprägte Stressreaktion hervorrufen. Mäuse werden in Stoffwechselkäfigen auf Metallgittern gehalten, um zusätzlich zur Überwachung der Futter- und Wasseraufnahme Urin und Kot aufzufangen. Darüber hinaus werden die Mäuse einzeln gehalten und es wird kein Nist-, Einstreu- oder Anreicherungs-Material zur Verfügung gestellt, was oft als Ursache für Kältestress angeführt wird, welcher sich auf das Wohlergehen der Tiere auswirkt. Wir haben daher versucht, den Stress bei der Haltung von Mäusen in Stoffwechselkäfigen zu reduzieren, indem wir einen innovativen Stoffwechselkäfig (IMC) mit einem kommerziell erhältlichen Stoffwechselkäfig der Tecniplast GmbH (TMC) und einem Kontrollkäfig verglichen haben. Für das Käfigdesign des IMC wurden wesentliche Refinement-Maßnahmen realisiert. Im Rahmen einer multifaktoriellen Beurteilung des Schweregrades wurden Parameter wie Körpergewicht, Körperzusammensetzung, Nahrungsaufnahme, Käfig- und Körperoberflächentemperatur (Wärmebildaufnahmen), mRNA-Expression von Uncoupling Protein 1 (Ucp1) im braunen Fettgewebe (BAT), Fur Score und fäkale Corticosteron-Metabolite (CMs) einbezogen. Weibliche und männliche C57BL/6J-Mäuse wurden für jeweils 24 Stunden entweder in konventionellen Macrolon-Käfigen (Kontrolle), IMC oder TMC zweimal untergebracht. Das Körpergewicht nahm in dem IMC weniger ab (Weibchen - 1. Haltung: -6,94%; 2. Haltung: -6,89%; Männchen - 1. Haltung: -8,08%; 2. Haltung: -5,82%) als in dem TMC (Weibchen - 1. Haltung: -13,2%; 2. Haltung: -15,0%; Männchen - 1. Haltung: -13,1%; 2. Haltung: -14,9%) und der IMC wies eine höhere Käfigtemperatur (Weibchen - 1. Haltung: 23,7 °C; 2. Haltung 23,5 °C; Männchen - 1. Haltung: 23,3 °C; 2. Haltung: 23,5 °C) im Vergleich zum TMC auf (Weibchen - 1. Haltung: 22,4 °C; 2. Haltung: 22,5 °C; Männchen - 1. Haltung: 22,6 °C; 2. Haltung: 22,4 °C). Die Konzentration der fäkalen Corticosteron-Metabolite im TMC (Weibchen - 1. Haltung: 1376 ng/g Trockengewicht (DW); 2. Haltung: 2098 ng/g DW; Männchen – 1. Haltung: 1030 ng/g DW; 2. Haltung: 1163 ng/g DW) war im Vergleich zur Kontrollkäfighaltung höher (Weibchen - 1. Haltung: 640 ng/g DW; 2. Haltung: 941 ng/g DW; Männchen - 1. Haltung: 504 ng/g DW; 2. Haltung: 537 ng/g DW). Unsere Ergebnisse zeigen das Stresspotenzial, welches durch die Haltung in Stoffwechselkäfigen ausgelöst wird, und dass durch die niedrigere Haltungstemperatur deutlich beeinflusst wird. Der IMC stellt einen ersten Versuch dar, den Kältestress während der Anwendung des Stoffwechselkäfigs zu reduzieren und dadurch tierschutzgerechtere Daten zu produzieren. KW - metabolic cage KW - laboratory mice KW - refinement KW - animal welfare KW - Tierschutz KW - Labormäuse KW - Stoffwechselkäfig KW - Refinement Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-611208 ER - TY - JOUR A1 - Witt, Barbara A1 - Stiboller, Michael A1 - Raschke, Stefanie A1 - Friese, Sharleen A1 - Ebert, Franziska A1 - Schwerdtle, Tanja T1 - Characterizing effects of excess copper levels in a human astrocytic cell line with focus on oxidative stress markers JF - Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements, GMS N2 - Background: Being an essential trace element, copper is involved in diverse physiological processes. However, excess levels might lead to adverse effects. Disrupted copper homeostasis, particularly in the brain, has been associated with human diseases including the neurodegenerative disorders Wilson and Alzheimer?s disease. In this context, astrocytes play an important role in the regulation of the copper homeostasis in the brain and likely in the prevention against neuronal toxicity, consequently pointing them out as a potential target for the neurotoxicity of copper. Major toxic mechanisms are discussed to be directed against mitochondria probably via oxidative stress. However, the toxic potential and mode of action of copper in astrocytes is poorly understood, so far. Methods: In this study, excess copper levels affecting human astrocytic cell model and their involvement in the neurotoxic mode of action of copper, as well as, effects on the homeostasis of other trace elements (Mn, Fe, Ca and Mg) were investigated. Results: Copper induced substantial cytotoxic effects in the human astrocytic cell line following 48 h incubation (EC30: 250 ?M) and affected mitochondrial function, as observed via reduction of mitochondrial membrane potential and increased ROS production, likely originating from mitochondria. Moreover, cellular GSH metabolism was altered as well. Interestingly, not only cellular copper levels were affected, but also the homeostasis of other elements (Ca, Fe and Mn) were disrupted. Conclusion: One potential toxic mode of action of copper seems to be effects on the mitochondria along with induction of oxidative stress in the human astrocytic cell model. Moreover, excess copper levels seem to interact with the homeostasis of other essential elements such as Ca, Fe and Mn. Disrupted element homeostasis might also contribute to the induction of oxidative stress, likely involved in the onset and progression of neurodegenerative disorders. These insights in the toxic mechanisms will help to develop ideas and approaches for therapeutic strategies against copper-mediated diseases. KW - Copper KW - Astrocytes KW - Toxicity KW - Mitochondria KW - ROS KW - Trace elements Y1 - 2021 U6 - https://doi.org/10.1016/j.jtemb.2021.126711 SN - 1878-3252 VL - 65 PB - Elsevier CY - München ER - TY - JOUR A1 - Witt, Barbara A1 - Schaumlöffel, Dirk A1 - Schwerdtle, Tanja T1 - Subcellular Localization of Copper BT - Cellular Bioimaging with Focus on Neurological Disorders JF - International Journal of Molecular Sciences N2 - As an essential trace element, copper plays a pivotal role in physiological body functions. In fact, dysregulated copper homeostasis has been clearly linked to neurological disorders including Wilson and Alzheimer’s disease. Such neurodegenerative diseases are associated with progressive loss of neurons and thus impaired brain functions. However, the underlying mechanisms are not fully understood. Characterization of the element species and their subcellular localization is of great importance to uncover cellular mechanisms. Recent research activities focus on the question of how copper contributes to the pathological findings. Cellular bioimaging of copper is an essential key to accomplish this objective. Besides information on the spatial distribution and chemical properties of copper, other essential trace elements can be localized in parallel. Highly sensitive and high spatial resolution techniques such as LA-ICP-MS, TEM-EDS, S-XRF and NanoSIMS are required for elemental mapping on subcellular level. This review summarizes state-of-the-art techniques in the field of bioimaging. Their strengths and limitations will be discussed with particular focus on potential applications for the elucidation of copper-related diseases. Based on such investigations, further information on cellular processes and mechanisms can be derived under physiological and pathological conditions. Bioimaging studies might enable the clarification of the role of copper in the context of neurodegenerative diseases and provide an important basis to develop therapeutic strategies for reduction or even prevention of copper-related disorders and their pathological consequences. KW - copper KW - cellular bioimaging KW - neurodegenerative diseases KW - copper-related disorders KW - SIMS techniques KW - TEM KW - S-XRF Y1 - 2020 U6 - https://doi.org/10.3390/ijms21072341 SN - 1422-0067 VL - 21 IS - 7 PB - Molecular Diversity Preservation International CY - Basel ER - TY - GEN A1 - Witt, Barbara A1 - Schaumlöffel, Dirk A1 - Schaumlöffel, Dirk A1 - Schwerdtle, Tanja T1 - Subcellular Localization of Copper BT - Cellular Bioimaging with Focus on Neurological Disorders T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - As an essential trace element, copper plays a pivotal role in physiological body functions. In fact, dysregulated copper homeostasis has been clearly linked to neurological disorders including Wilson and Alzheimer’s disease. Such neurodegenerative diseases are associated with progressive loss of neurons and thus impaired brain functions. However, the underlying mechanisms are not fully understood. Characterization of the element species and their subcellular localization is of great importance to uncover cellular mechanisms. Recent research activities focus on the question of how copper contributes to the pathological findings. Cellular bioimaging of copper is an essential key to accomplish this objective. Besides information on the spatial distribution and chemical properties of copper, other essential trace elements can be localized in parallel. Highly sensitive and high spatial resolution techniques such as LA-ICP-MS, TEM-EDS, S-XRF and NanoSIMS are required for elemental mapping on subcellular level. This review summarizes state-of-the-art techniques in the field of bioimaging. Their strengths and limitations will be discussed with particular focus on potential applications for the elucidation of copper-related diseases. Based on such investigations, further information on cellular processes and mechanisms can be derived under physiological and pathological conditions. Bioimaging studies might enable the clarification of the role of copper in the context of neurodegenerative diseases and provide an important basis to develop therapeutic strategies for reduction or even prevention of copper-related disorders and their pathological consequences. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 862 KW - copper KW - cellular bioimaging KW - neurodegenerative diseases KW - copper-related disorders KW - SIMS techniques KW - TEM KW - S-XRF Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-459544 SN - 1866-8372 IS - 862 ER -