@article{vonLoeffelholzLieskeNeuschaeferRubeetal.2017, author = {von Loeffelholz, Christian and Lieske, Stefanie and Neuschaefer-Rube, Frank and Willmes, Diana M. and Raschzok, Nathanael and Sauer, Igor M. and K{\"o}nig, J{\"o}rg and Fromm, Martin F. and Horn, Paul and Chatzigeorgiou, Antonios and Pathe-Neuschaefer-Rube, Andrea and Jordan, Jens and Pfeiffer, Andreas F. H. and Mingrone, Geltrude and Bornstein, Stefan R. and Stroehle, Peter and Harms, Christoph and Wunderlich, F. Thomas and Helfand, Stephen L. and Bernier, Michel and de Cabo, Rafael and Shulman, Gerald I. and Chavakis, Triantafyllos and P{\"u}schel, Gerhard Paul and Birkenfeld, Andreas L.}, title = {The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism}, series = {Hepatology}, volume = {66}, journal = {Hepatology}, number = {2}, publisher = {Wiley}, address = {Hoboken}, issn = {0270-9139}, doi = {10.1002/hep.29089}, pages = {616 -- 630}, year = {2017}, abstract = {Reduced expression of the Indy ("I am Not Dead, Yet") gene in lower organisms promotes longevity in a manner akin to caloric restriction. Deletion of the mammalian homolog of Indy (mIndy, Slc13a5) encoding for a plasma membrane-associated citrate transporter expressed highly in the liver, protects mice from high-fat diet-induced and aging-induced obesity and hepatic fat accumulation through a mechanism resembling caloric restriction. We studied a possible role of mIndy in human hepatic fat metabolism. In obese, insulin-resistant patients with nonalcoholic fatty liver disease, hepatic mIndy expression was increased and mIndy expression was also independently associated with hepatic steatosis. In nonhuman primates, a 2-year high-fat, high-sucrose diet increased hepatic mIndy expression. Liver microarray analysis showed that high mIndy expression was associated with pathways involved in hepatic lipid metabolism and immunological processes. Interleukin-6 (IL-6) was identified as a regulator of mIndy by binding to its cognate receptor. Studies in human primary hepatocytes confirmed that IL-6 markedly induced mIndy transcription through the IL-6 receptor and activation of the transcription factor signal transducer and activator of transcription 3, and a putative start site of the human mIndy promoter was determined. Activation of the IL-6-signal transducer and activator of transcription 3 pathway stimulated mIndy expression, enhanced cytoplasmic citrate influx, and augmented hepatic lipogenesis in vivo. In contrast, deletion of mIndy completely prevented the stimulating effect of IL-6 on citrate uptake and reduced hepatic lipogenesis. These data show that mIndy is increased in liver of obese humans and nonhuman primates with NALFD. Moreover, our data identify mIndy as a target gene of IL-6 and determine novel functions of IL-6 through mINDY. Conclusion: Targeting human mINDY may have therapeutic potential in obese patients with nonalcoholic fatty liver disease. German Clinical Trials Register: DRKS00005450.}, language = {en} } @article{NeuschaeferRubeLieskeKunaetal.2014, author = {Neuschaefer-Rube, Frank and Lieske, Stefanie and Kuna, Manuela and Henkel, Janin and Perry, Rachel J. and Erion, Derek M. and Pesta, Dominik and Willmes, Diana M. and Brachs, Sebastian and von Loeffelholz, Christian and Tolkachov, Alexander and Schupp, Michael and Pathe-Neuschaefer-Rube, Andrea and Pfeiffer, Andreas F. H. and Shulman, Gerald I. and P{\"u}schel, Gerhard Paul and Birkenfeld, Andreas L.}, title = {The mammalian INDY homolog is induced by CREB in a rat model of type 2 diabetes}, series = {Diabetes : a journal of the American Diabetes Association}, volume = {63}, journal = {Diabetes : a journal of the American Diabetes Association}, number = {3}, publisher = {American Diabetes Association}, address = {Alexandria}, issn = {0012-1797}, pages = {1048 -- 1057}, year = {2014}, language = {en} } @article{GarciaSteinigerReichetal.2006, author = {Garcia, A. L. and Steiniger, J. and Reich, S. C. and Weickert, M. O. and Harsch, I. and Machowetz, A. and Mohlig, M. and Spranger, Joachim and Rudovich, N. N. and Meuser, F. and Doerfer, J. and Katz, N. and Speth, M. and Zunft, Hans-Joachim Franz and Pfeiffer, Andreas F. H. and Koebnick, Corinna}, title = {Arabinoxylan fibre consumption improved glucose metabolism, but did not affect serum adipokines in subjects with impaired glucose tolerance}, series = {Hormone and metabolic research}, volume = {38}, journal = {Hormone and metabolic research}, number = {2}, publisher = {Thieme}, address = {Stuttgart}, issn = {0018-5043}, doi = {10.1055/s-2006-955089}, pages = {761 -- 766}, year = {2006}, abstract = {The consumption of arabinoxylan, a soluble fibre fraction, has been shown to improve glycemic control in type 2 diabetic subjects. Soluble dietary fibre may modulate gastrointestinal or adipose tissue hormones regulating food intake. The present study investigated the effects of arabinoxylan consumption on serum glucose, insulin, lipids, leptin, adiponectin and resistin in subjects with impaired glucose tolerance. In a randomized, single-blind, controlled, crossover intervention trial, 11 adults consumed white bread rolls as either placebo or supplemented with 15g arabinoxylan for 6 weeks with a 6-week washout period. Fasting serum glucose, insulin, triglycerides, unesterified fatty acids, apolipoprotein A1 and B, adiponectin, resistin and leptin were assessed before and after intervention. Fasting serum glucose, serum triglycerides and apolipoprotein A-1 were significantly lower during arabinoxylan consumption compared to placebo (p = 0.029, p = 0.047; p = 0.029, respectively). No effects of arabinoxylan were observed for insulin, adiponectin, leptin and resistin as well as for apolipoprotein B, and unesterified fatty acids. In conclusion, the consumption of AX in subjects with impaired glucose tolerance improved fasting serum glucose, and triglycerides. However, this beneficial effect was not accompanied by changes in fasting adipokine concentrations.}, language = {en} } @article{ThierbachSchulzVoigtetal.2004, author = {Thierbach, Rene and Schulz, Tim Julius and Voigt, Aanja and Drewes, Gunnar and Isken, F. and Pfeiffer, Andreas F. H. and Ristow, Michael and Steinberg, Pablo}, title = {Targeted disruption of frataxin in hepatocytes causes spontaneous neoplasia accompanied by increased ROS formation}, issn = {0028-1298}, year = {2004}, language = {en} } @article{MoehligFloeterSprangeretal.2006, author = {Moehlig, M. and Floeter, A. and Spranger, Joachim and Weickert, Martin O. and Schill, T. and Schloesser, H. W. and Brabant, G. and Pfeiffer, Andreas F. H. and Selbig, Joachim and Schoefl, C.}, title = {Predicting impaired glucose metabolism in women with polycystic ovary syndrome by decision tree modelling}, series = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, volume = {49}, journal = {Diabetologia : journal of the European Association for the Study of Diabetes (EASD)}, publisher = {Springer}, address = {Berlin}, issn = {0012-186X}, doi = {10.1007/s00125-006-0395-0}, pages = {2572 -- 2579}, year = {2006}, abstract = {Aims/hypothesis Polycystic ovary syndrome (PCOS) is a risk factor of type 2 diabetes. Screening for impaired glucose metabolism (IGM) with an OGTT has been recommended, but this is relatively time-consuming and inconvenient. Thus, a strategy that could minimise the need for an OGTT would be beneficial. Materials and methods Consecutive PCOS patients (n=118) with fasting glucose < 6.1 mmol/l were included in the study. Parameters derived from medical history, clinical examination and fasting blood samples were assessed by decision tree modelling for their ability to discriminate women with IGM (2-h OGTT value >= 7.8 mmol/l) from those with NGT. Results According to the OGTT results, 93 PCOS women had NGT and 25 had IGM. The best decision tree consisted of HOMA-IR, the proinsulin:insulin ratio, proinsulin, 17-OH progesterone and the ratio of luteinising hormone:follicle-stimulating hormone. This tree identified 69 women with NGT. The remaining 49 women included all women with IGM (100\% sensitivity, 74\% specificity to detect IGM). Pruning this tree to three levels still identified 53 women with NGT (100\% sensitivity, 57\% specificity to detect IGM). Restricting the data matrix used for tree modelling to medical history and clinical parameters produced a tree using BMI, waist circumference and WHR. Pruning this tree to two levels separated 27 women with NGT (100\% sensitivity, 29\% specificity to detect IGM). The validity of both trees was tested by a leave-10\%-out cross-validation. Conclusions/interpretation Decision trees are useful tools for separating PCOS women with NGT from those with IGM. They can be used for stratifying the metabolic screening of PCOS women, whereby the number of OGTTs can be markedly reduced.}, language = {en} } @article{SchenkEichelmannSchulzeetal.2019, author = {Schenk, Matthew and Eichelmann, Fabian and Schulze, Matthias Bernd and Rudovich, Natalia and Pfeiffer, Andreas F. H. and di Giuseppe, Romina and B{\"o}ing, Heiner and Aleksandrova, Krasimira}, title = {Reproducibility of novel immune-inflammatory biomarkers over 4 months}, series = {Biomarkers in medicine}, volume = {13}, journal = {Biomarkers in medicine}, number = {8}, publisher = {Future Medicine}, address = {London}, issn = {1752-0363}, doi = {10.2217/bmm-2018-0351}, pages = {639 -- 648}, year = {2019}, abstract = {Aim: Assessment of the feasibility and reliability of immune-inflammatory biomarker measurements. Methods: The following biomarkers were assessed in 207 predominantly healthy participants at baseline and after 4 months: MMF, TGF-beta, suPAR and clusterin. Results: Intraclass correlation coefficients (95\% CIs) ranged from good for TGF-beta (0.75 [95\% CI: 0.33-0.90]) to excellent for MMF (0.81 [95\% CI: 0.64-0.90]), clusterin (0.83 [95\% CI: 0.78-0.87]) and suPAR (0.91 [95\% CI: 0.88-0.93]). Measurement of TGF-beta was challenged by the large number of values below the detection limit. Conclusion: Single measurements of suPAR, clusterin and MMF could serve as feasible and reliable biomarkers of immune-inflammatory pathways in biomedical research.}, language = {en} } @article{HansenKraenkelKempsetal.2019, author = {Hansen, Dominique and Kraenkel, Nicolle and Kemps, Hareld and Wilhelm, Matthias and Abreu, Ana and Pfeiffer, Andreas F. H. and Jordao, Alda and Cornelissen, Veronique and V{\"o}ller, Heinz}, title = {Management of patients with type 2 diabetes in cardiovascular rehabilitation}, series = {European journal of preventive cardiology : the official ESC journal for primary \& secondary cardiovascular prevention, rehabilitation and sports cardiology}, volume = {26}, journal = {European journal of preventive cardiology : the official ESC journal for primary \& secondary cardiovascular prevention, rehabilitation and sports cardiology}, number = {2_SUPPL}, publisher = {Sage Publ.}, address = {London}, issn = {2047-4873}, doi = {10.1177/2047487319882820}, pages = {133 -- 144}, year = {2019}, abstract = {The clinical benefits of rehabilitation in cardiovascular disease are well established. Among cardiovascular disease patients, however, patients with type 2 diabetes mellitus require a distinct approach. Specific challenges to clinicians and healthcare professionals in patients with type 2 diabetes include the prevalence of peripheral and autonomic neuropathy, retinopathy, nephropathy, but also the intake of glucose-lowering medication. In addition, the psychosocial wellbeing, driving ability and/or occupational status can be affected by type 2 diabetes. As a result, the target parameters of cardiovascular rehabilitation and the characteristics of the cardiovascular rehabilitation programme in patients with type 2 diabetes often require significant reconsideration and a multidisciplinary approach. This review explains how to deal with diabetes-associated comorbidities in the intake screening of patients with type 2 diabetes entering a cardiovascular rehabilitation programme. Furthermore, we discuss diabetes-specific target parameters and characteristics of cardiovascular rehabilitation programmes for patients with type 2 diabetes in a multidisciplinary context, including the implementation of guideline-directed medical therapy.}, language = {en} } @article{MeyerMarkovaPohletal.2018, author = {Meyer, S{\"o}ren and Markova, Mariya and Pohl, Gabriele and Marschall, Talke Anu and Pivovarova, Olga and Pfeiffer, Andreas F. H. and Schwerdtle, Tanja}, title = {Development, validation and application of an ICP-MS/MS method to quantify minerals and (ultra-)trace elements in human serum}, series = {Journal of trace elements in medicine and biology}, volume = {49}, journal = {Journal of trace elements in medicine and biology}, publisher = {Elsevier GMBH}, address = {M{\"u}nchen}, issn = {0946-672X}, doi = {10.1016/j.jtemb.2018.05.012}, pages = {157 -- 163}, year = {2018}, abstract = {Multi-element determination in human samples is very challenging. Especially in human intervention studies sample volumes are often limited to a few microliters and due to the high number of samples a high-throughput is indispensable. Here, we present a state-of-the-art ICP-MS/MS-based method for the analysis of essential (trace) elements, namely Mg, Ca, Fe, Cu, Zn, Mo, Se and I, as well as food-relevant toxic elements such as As and Cd. The developed method was validated regarding linearity of the calibration curves, method LODs and LOQs, selectivity and trueness as well as precision. The established reliable method was applied to quantify the element serum concentrations of participants of a human intervention study (LeguAN). The participants received isocaloric diets, either rich in plant protein or in animal protein. While the serum concentrations of Mg and Mo increased in participants receiving the plant protein-based diet (above all legumes), the Se concentration in serum decreased. In contrast, the animal protein-based diet, rich in meat and dairy products, resulted in an increased Se concentration in serum.}, language = {en} } @misc{HischeLarhlimiSchwarzetal.2012, author = {Hische, Manuela and Larhlimi, Abdelhalim and Schwarz, Franziska and Fischer-Rosinsk{\´y}, Antje and Bobbert, Thomas and Assmann, Anke and Catchpole, Gareth S. and Pfeiffer, Andreas F. H. and Willmitzer, Lothar and Selbig, Joachim and Spranger, Joachim}, title = {A distinct metabolic signature predictsdevelopment of fasting plasma glucose}, series = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam : Mathematisch Naturwissenschaftliche Reihe}, number = {850}, issn = {1866-8372}, doi = {10.25932/publishup-42740}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-427400}, pages = {12}, year = {2012}, abstract = {Background High blood glucose and diabetes are amongst the conditions causing the greatest losses in years of healthy life worldwide. Therefore, numerous studies aim to identify reliable risk markers for development of impaired glucose metabolism and type 2 diabetes. However, the molecular basis of impaired glucose metabolism is so far insufficiently understood. The development of so called 'omics' approaches in the recent years promises to identify molecular markers and to further understand the molecular basis of impaired glucose metabolism and type 2 diabetes. Although univariate statistical approaches are often applied, we demonstrate here that the application of multivariate statistical approaches is highly recommended to fully capture the complexity of data gained using high-throughput methods. Methods We took blood plasma samples from 172 subjects who participated in the prospective Metabolic Syndrome Berlin Potsdam follow-up study (MESY-BEPO Follow-up). We analysed these samples using Gas Chromatography coupled with Mass Spectrometry (GC-MS), and measured 286 metabolites. Furthermore, fasting glucose levels were measured using standard methods at baseline, and after an average of six years. We did correlation analysis and built linear regression models as well as Random Forest regression models to identify metabolites that predict the development of fasting glucose in our cohort. Results We found a metabolic pattern consisting of nine metabolites that predicted fasting glucose development with an accuracy of 0.47 in tenfold cross-validation using Random Forest regression. We also showed that adding established risk markers did not improve the model accuracy. However, external validation is eventually desirable. Although not all metabolites belonging to the final pattern are identified yet, the pattern directs attention to amino acid metabolism, energy metabolism and redox homeostasis. Conclusions We demonstrate that metabolites identified using a high-throughput method (GC-MS) perform well in predicting the development of fasting plasma glucose over several years. Notably, not single, but a complex pattern of metabolites propels the prediction and therefore reflects the complexity of the underlying molecular mechanisms. This result could only be captured by application of multivariate statistical approaches. Therefore, we highly recommend the usage of statistical methods that seize the complexity of the information given by high-throughput methods.}, language = {en} } @article{FreySprangerHenzeetal.2009, author = {Frey, Simone K. and Spranger, Joachim and Henze, Andrea and Pfeiffer, Andreas F. H. and Schweigert, Florian J. and Raila, Jens}, title = {Factors that influence retinol-binding protein 4-transthyretin interaction are not altered in overweight subjects and overweight subjects with type 2 diabetes mellitus}, issn = {0026-0495}, doi = {10.1016/j.metabol.2009.05.003}, year = {2009}, abstract = {Retinol-binding protein 4 (RBP4) is an adipokine bound in plasma to transthyretin (TTR), which prevents its glomerular filtration and subsequent catabolism in the kidney. Alterations of this interaction have been Suggested to be implicated in the elevation of RBP4 that are thought to contribute to the development Of insulin resistance associated with obesity and type 2 diabetes mellitus (T2DM). However, the factors linking RBP4 to TTR in humans are not clear. Therefore, this Study evaluated parameters influencing the RBP4-TTR interaction and their relation to obesity and T2DM. The RBP4 and TTR levels were quantified in plasma of 16 lean controls, 28 overweight controls, and 14 overweight T2DM patients by enzyme-linked immunosorbent assay. Transthyretin isoforms involved in RBP4 binding were determined by linear matrix-assisted laser desorption/ionization-time of flight-mass spectrometry after RBP4 coimmunoprecipitation. Holo-RBP4 (retinol-bound) and apo-RBP4 (retinol-free) were assessed by immunoblotting using nondenaturating polyacrylamide gel electrophoresis. Plasma levels of both RBP4 and TTR did not differ among the groups of lean controls, overweight controls, and overweight T2DM subjects. Using RBP4 immunoprecipitation, 4 mass signals were observed for TTR representing native, S-cysteinylated, S-cysteinglycinylated, and S-glutathionylated TTR. No differences in peak intensity of TTR isoforms were observed among the groups. Moreover, no differences in the ratio of holo- and apo-RBP4 were evident. The results suggest that circulating RBP4 and TTR were not affected by human obesity or T2DM, which might be attributed to the absence of alterations of TTR isoforms and the ratio of holo- and apo-RBP4 that might modify the TTR-RBP4 interaction.}, language = {en} } @article{BobbertRailaSchwarzetal.2010, author = {Bobbert, Thomas and Raila, Jens and Schwarz, Franziska and Mai, Knut and Henze, Andrea and Pfeiffer, Andreas F. H. and Schweigert, Florian J. and Spranger, Joachim}, title = {Relation between retinol, retinol-binding protein 4, transthyretin and carotid intima media thickness}, issn = {0021-9150}, doi = {10.1016/j.atherosclerosis.2010.07.063}, year = {2010}, abstract = {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.}, language = {en} } @article{HischeLuisDominguezPfeifferetal.2010, author = {Hische, Manuela and Luis-Dominguez, Olga and Pfeiffer, Andreas F. H. and Schwarz, Peter E. and Selbig, Joachim and Spranger, Joachim}, title = {Decision trees as a simple-to-use and reliable tool to identify individuals with impaired glucose metabolism or type 2 diabetes mellitus}, issn = {0804-4643}, doi = {10.1530/Eje-10-0649}, year = {2010}, abstract = {Objective: The prevalence of unknown impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or type 2 diabetes mellitus (T2DM) is high. Numerous studies demonstrated that IFG, IGT, or T2DM are associated with increased cardiovascular risk, therefore an improved identification strategy would be desirable. The objective of this study was to create a simple and reliable tool to identify individuals with impaired glucose metabolism (IGM). Design and methods: A cohort of 1737 individuals (1055 controls, 682 with previously unknown IGM) was screened by 75 g oral glucose tolerance test (OGTT). Supervised machine learning was used to automatically generate decision trees to identify individuals with IGM. To evaluate the accuracy of identification, a tenfold cross-validation was performed. Resulting trees were subsequently re-evaluated in a second, independent cohort of 1998 individuals (1253 controls, 745 unknown IGM). Results: A clinical decision tree included age and systolic blood pressure (sensitivity 89.3\%, specificity 37.4\%, and positive predictive value (PPV) 48.0\%), while a tree based on clinical and laboratory data included fasting glucose and systolic blood pressure (sensitivity 89.7\%, specificity 54.6\%, and PPV 56.2\%). The inclusion of additional parameters did not improve test quality. The external validation approach confirmed the presented decision trees. Conclusion: We proposed a simple tool to identify individuals with existing IGM. From a practical perspective, fasting blood glucose and blood pressure measurements should be regularly measured in all individuals presenting in outpatient clinics. An OGTT appears to be useful only if the subjects are older than 48 years or show abnormalities in fasting glucose or blood pressure.}, language = {en} } @article{AllanBossdorfDormannetal.2014, author = {Allan, Eric and Bossdorf, Oliver and Dormann, Carsten F. and Prati, Daniel and Gossner, Martin M. and Tscharntke, Teja and Bl{\"u}thgen, Nico and Bellach, Michaela and Birkhofer, Klaus and Boch, Steffen and B{\"o}hm, Stefan and B{\"o}rschig, Carmen and Chatzinotas, Antonis and Christ, Sabina and Daniel, Rolf and Diek{\"o}tter, Tim and Fischer, Christiane and Friedl, Thomas and Glaser, Karin and Hallmann, Christine and Hodac, Ladislav and H{\"o}lzel, Norbert and Jung, Kirsten and Klein, Alexandra Maria and Klaus, Valentin H. and Kleinebecker, Till and Krauss, Jochen and Lange, Markus and Morris, E. Kathryn and M{\"u}ller, J{\"o}rg and Nacke, Heiko and Pasalic, Esther and Rillig, Matthias C. and Rothenwoehrer, Christoph and Schally, Peter and Scherber, Christoph and Schulze, Waltraud X. and Socher, Stephanie A. and Steckel, Juliane and Steffan-Dewenter, Ingolf and T{\"u}rke, Manfred and Weiner, Christiane N. and Werner, Michael and Westphal, Catrin and Wolters, Volkmar and Wubet, Tesfaye and Gockel, Sonja and Gorke, Martin and Hemp, Andreas and Renner, Swen C. and Sch{\"o}ning, Ingo and Pfeiffer, Simone and K{\"o}nig-Ries, Birgitta and Buscot, Francois and Linsenmair, Karl Eduard and Schulze, Ernst-Detlef and Weisser, Wolfgang W. and Fischer, Markus}, title = {Interannual variation in land-use intensity enhances grassland multidiversity}, series = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {111}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, number = {1}, publisher = {National Acad. of Sciences}, address = {Washington}, issn = {0027-8424}, doi = {10.1073/pnas.1312213111}, pages = {308 -- 313}, year = {2014}, abstract = {Although temporal heterogeneity is a well-accepted driver of biodiversity, effects of interannual variation in land-use intensity (LUI) have not been addressed yet. Additionally, responses to land use can differ greatly among different organisms; therefore, overall effects of land-use on total local biodiversity are hardly known. To test for effects of LUI (quantified as the combined intensity of fertilization, grazing, and mowing) and interannual variation in LUI (SD in LUI across time), we introduce a unique measure of whole-ecosystem biodiversity, multidiversity. This synthesizes individual diversity measures across up to 49 taxonomic groups of plants, animals, fungi, and bacteria from 150 grasslands. Multidiversity declined with increasing LUI among grasslands, particularly for rarer species and aboveground organisms, whereas common species and belowground groups were less sensitive. However, a high level of interannual variation in LUI increased overall multidiversity at low LUI and was even more beneficial for rarer species because it slowed the rate at which the multidiversity of rare species declined with increasing LUI. In more intensively managed grasslands, the diversity of rarer species was, on average, 18\% of the maximum diversity across all grasslands when LUI was static over time but increased to 31\% of the maximum when LUI changed maximally over time. In addition to decreasing overall LUI, we suggest varying LUI across years as a complementary strategy to promote biodiversity conservation.}, language = {en} } @article{SchulzThierbachVoigtetal.2006, author = {Schulz, Tim Julius and Thierbach, Ren{\`e} and Voigt, Anja and Drewes, Gunnar and Mietzner, Brun and Steinberg, Pablo and Pfeiffer, Andreas F. H. and Ristow, Michael}, title = {Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth : Otto Warburg revisited}, doi = {10.1074/jbc.M511064200}, year = {2006}, abstract = {More than 80 years ago Otto Warburg suggested that cancer might be caused by a decrease in mitochondrial energy metabolism paralleled by an increase in glycolytic flux. In later years, it was shown that cancer cells exhibit multiple alterations in mitochondrial content, structure, function, and activity. We have stably overexpressed the Friedreich ataxia-associated protein frataxin in several colon cancer cell lines. These cells have increased oxidative metabolism, as shown by concurrent increases in aconitase activity, mitochondrial membrane potential, cellular respiration, and ATP content. Consistent with Warburg's hypothesis, we found that frataxin-overexpressing cells also have decreased growth rates and increased population doubling times, show inhibited colony formation capacity in soft agar assays, and exhibit a reduced capacity for tumor formation when injected into nude mice. Furthermore, overexpression of frataxin leads to an increased phosphorylation of the tumor suppressor p38 mitogen-activated protein kinase, as well as decreased phosphorylation of extracellular signal-regulated kinase. Taken together, these results support the view that an increase in oxidative metabolism induced by mitochondrial frataxin may inhibit cancer growth in mammals}, language = {en} } @article{ThierbachSchulzIskenetal.2005, author = {Thierbach, Ren{\`e} and Schulz, Tim Julius and Isken, Frank and Voigt, Aanja and Mietzner, Brun and Drewes, Gunnar and von Kleist-Retzow, J{\"u}rgen-Christoph and Wiesner, Rudolf J. and Magnuson, Mark A. and Puccio, Helene and Pfeiffer, Andreas F. H. and Steinberg, Pablo and Ristow, Michael}, title = {Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span and tumor growth in mice}, year = {2005}, abstract = {We have disrupted expression of the mitochondrial Friedreich ataxia protein frataxin specifically in murine hepatocytes to generate mice with impaired mitochondrial function and decreased oxidative phosphorylation. These animals have a reduced life span and develop multiple hepatic tumors. Livers also show increased oxidative stress, impaired respiration and reduced ATP levels paralleled by reduced activity of iron-sulfur cluster (Fe/S) containing proteins (ISP), which all leads to increased hepatocyte turnover by promoting both apoptosis and proliferation. Accordingly, phosphorylation of the stress-inducible p38 MAP kinase was found to be specifically impaired following disruption of frataxin. Taken together, these findings indicate that frataxin may act as a mitochondrial tumor suppressor protein in mammals}, language = {en} } @article{KoelmanPivovarovaRamichPfeifferetal.2019, author = {Koelman, Liselot A. and Pivovarova-Ramich, Olga and Pfeiffer, Andreas F. H. and Grune, Tilman and Aleksandrova, Krasimira}, title = {Cytokines for evaluation of chronic inflammatory status in ageing research}, series = {Immunity \& Ageing}, volume = {16}, journal = {Immunity \& Ageing}, publisher = {BMC}, address = {London}, issn = {1742-4933}, doi = {10.1186/s12979-019-0151-1}, pages = {12}, year = {2019}, abstract = {Background: There is a growing interest in the role of inflammageing for chronic disease development. Cytokines are potent soluble immune mediators that can be used as target biomarkers of inflammageing; however, their measurement in human samples has been challenging. This study aimed to assess the reliability of a pro- and anti-inflammatory cytokine panel in a sample of healthy people measured with a novel electrochemiluminescent multiplex immunoassay platform (Meso Scale Discovery, MSD), and to characterize their associations with metabolic and inflammatory phenotypes.}, language = {en} } @misc{KesslerHornemannRudovichetal.2020, author = {Kessler, Katharina and Hornemann, Silke and Rudovich, Natalia and Weber, Daniela and Grune, Tilman and Kramer, Achim and Pfeiffer, Andreas F. H. and Pivovarova-Ramich, Olga}, title = {Saliva samples as a tool to study the effect of meal timing on metabolic and inflammatory biomarkers}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe}, number = {2}, issn = {1866-8372}, doi = {10.25932/publishup-51207}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-512079}, pages = {14}, year = {2020}, abstract = {Meal timing affects metabolic regulation in humans. Most studies use blood samples fortheir investigations. Saliva, although easily available and non-invasive, seems to be rarely used forchrononutritional studies. In this pilot study, we tested if saliva samples could be used to studythe effect of timing of carbohydrate and fat intake on metabolic rhythms. In this cross-over trial, 29 nonobese men were randomized to two isocaloric 4-week diets: (1) carbohydrate-rich meals until13:30 and high-fat meals between 16:30 and 22:00 or (2) the inverse order of meals. Stimulated salivasamples were collected every 4 h for 24 h at the end of each intervention, and levels of hormones andinflammatory biomarkers were assessed in saliva and blood. Cortisol, melatonin, resistin, adiponectin, interleukin-6 and MCP-1 demonstrated distinct diurnal variations, mirroring daytime reports inblood and showing significant correlations with blood levels. The rhythm patterns were similar forboth diets, indicating that timing of carbohydrate and fat intake has a minimal effect on metabolicand inflammatory biomarkers in saliva. Our study revealed that saliva is a promising tool for thenon-invasive assessment of metabolic rhythms in chrononutritional studies, but standardisation of sample collection is needed in out-of-lab studies.}, language = {en} } @article{KesslerHornemannRudovichetal.2020, author = {Kessler, Katharina and Hornemann, Silke and Rudovich, Natalia and Weber, Daniela and Grune, Tilman and Kramer, Achim and Pfeiffer, Andreas F. H. and Pivovarova-Ramich, Olga}, title = {Saliva samples as a tool to study the effect of meal timing on metabolic and inflammatory biomarkers}, series = {Nutrients}, journal = {Nutrients}, number = {2}, publisher = {MDPI}, address = {Basel}, issn = {2072-6643}, doi = {10.3390/nu12020340}, pages = {1 -- 12}, year = {2020}, abstract = {Meal timing affects metabolic regulation in humans. Most studies use blood samples fortheir investigations. Saliva, although easily available and non-invasive, seems to be rarely used forchrononutritional studies. In this pilot study, we tested if saliva samples could be used to studythe effect of timing of carbohydrate and fat intake on metabolic rhythms. In this cross-over trial, 29 nonobese men were randomized to two isocaloric 4-week diets: (1) carbohydrate-rich meals until13:30 and high-fat meals between 16:30 and 22:00 or (2) the inverse order of meals. Stimulated salivasamples were collected every 4 h for 24 h at the end of each intervention, and levels of hormones andinflammatory biomarkers were assessed in saliva and blood. Cortisol, melatonin, resistin, adiponectin, interleukin-6 and MCP-1 demonstrated distinct diurnal variations, mirroring daytime reports inblood and showing significant correlations with blood levels. The rhythm patterns were similar forboth diets, indicating that timing of carbohydrate and fat intake has a minimal effect on metabolicand inflammatory biomarkers in saliva. Our study revealed that saliva is a promising tool for thenon-invasive assessment of metabolic rhythms in chrononutritional studies, but standardisation of sample collection is needed in out-of-lab studies.}, language = {en} }