TY - JOUR A1 - von Loeffelholz, Christian A1 - Lieske, Stefanie A1 - Neuschaefer-Rube, Frank A1 - Willmes, Diana M. A1 - Raschzok, Nathanael A1 - Sauer, Igor M. A1 - König, Jörg A1 - Fromm, Martin F. A1 - Horn, Paul A1 - Chatzigeorgiou, Antonios A1 - Pathe-Neuschaefer-Rube, Andrea A1 - Jordan, Jens A1 - Pfeiffer, Andreas F. H. A1 - Mingrone, Geltrude A1 - Bornstein, Stefan R. A1 - Stroehle, Peter A1 - Harms, Christoph A1 - Wunderlich, F. Thomas A1 - Helfand, Stephen L. A1 - Bernier, Michel A1 - de Cabo, Rafael A1 - Shulman, Gerald I. A1 - Chavakis, Triantafyllos A1 - Püschel, Gerhard Paul A1 - Birkenfeld, Andreas L. T1 - The human longevity gene homolog INDY and interleukin-6 interact in hepatic lipid metabolism BT - official journal of the American Association for the Study of Liver Diseases JF - Hepatology N2 - 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. Y1 - 2017 U6 - https://doi.org/10.1002/hep.29089 SN - 0270-9139 SN - 1527-3350 VL - 66 IS - 2 SP - 616 EP - 630 PB - Wiley CY - Hoboken ER - TY - JOUR A1 - Hansen, Dominique A1 - Kraenkel, Nicolle A1 - Kemps, Hareld A1 - Wilhelm, Matthias A1 - Abreu, Ana A1 - Pfeiffer, Andreas F. H. A1 - Jordao, Alda A1 - Cornelissen, Veronique A1 - Völler, Heinz T1 - Management of patients with type 2 diabetes in cardiovascular rehabilitation JF - European journal of preventive cardiology : the official ESC journal for primary & secondary cardiovascular prevention, rehabilitation and sports cardiology N2 - 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. KW - Diabetes KW - cardiovascular rehabilitation KW - intake screening KW - exercise Y1 - 2019 U6 - https://doi.org/10.1177/2047487319882820 SN - 2047-4873 SN - 2047-4881 VL - 26 IS - 2_SUPPL SP - 133 EP - 144 PB - Sage Publ. CY - London ER - TY - JOUR A1 - Hische, Manuela A1 - Luis-Dominguez, Olga A1 - Pfeiffer, Andreas F. H. A1 - Schwarz, Peter E. A1 - Selbig, Joachim A1 - Spranger, Joachim T1 - Decision trees as a simple-to-use and reliable tool to identify individuals with impaired glucose metabolism or type 2 diabetes mellitus N2 - 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. Y1 - 2010 UR - http://www.eje-online.org/ U6 - https://doi.org/10.1530/Eje-10-0649 SN - 0804-4643 ER - TY - JOUR A1 - Allan, Eric A1 - Bossdorf, Oliver A1 - Dormann, Carsten F. A1 - Prati, Daniel A1 - Gossner, Martin M. A1 - Tscharntke, Teja A1 - Blüthgen, Nico A1 - Bellach, Michaela A1 - Birkhofer, Klaus A1 - Boch, Steffen A1 - Böhm, Stefan A1 - Börschig, Carmen A1 - Chatzinotas, Antonis A1 - Christ, Sabina A1 - Daniel, Rolf A1 - Diekötter, Tim A1 - Fischer, Christiane A1 - Friedl, Thomas A1 - Glaser, Karin A1 - Hallmann, Christine A1 - Hodac, Ladislav A1 - Hölzel, Norbert A1 - Jung, Kirsten A1 - Klein, Alexandra Maria A1 - Klaus, Valentin H. A1 - Kleinebecker, Till A1 - Krauss, Jochen A1 - Lange, Markus A1 - Morris, E. Kathryn A1 - Müller, Jörg A1 - Nacke, Heiko A1 - Pasalic, Esther A1 - Rillig, Matthias C. A1 - Rothenwoehrer, Christoph A1 - Schally, Peter A1 - Scherber, Christoph A1 - Schulze, Waltraud X. A1 - Socher, Stephanie A. A1 - Steckel, Juliane A1 - Steffan-Dewenter, Ingolf A1 - Türke, Manfred A1 - Weiner, Christiane N. A1 - Werner, Michael A1 - Westphal, Catrin A1 - Wolters, Volkmar A1 - Wubet, Tesfaye A1 - Gockel, Sonja A1 - Gorke, Martin A1 - Hemp, Andreas A1 - Renner, Swen C. A1 - Schöning, Ingo A1 - Pfeiffer, Simone A1 - König-Ries, Birgitta A1 - Buscot, Francois A1 - Linsenmair, Karl Eduard A1 - Schulze, Ernst-Detlef A1 - Weisser, Wolfgang W. A1 - Fischer, Markus T1 - Interannual variation in land-use intensity enhances grassland multidiversity JF - Proceedings of the National Academy of Sciences of the United States of America N2 - 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. KW - biodiversity loss KW - agricultural grasslands KW - Biodiversity Exploratories Y1 - 2014 U6 - https://doi.org/10.1073/pnas.1312213111 SN - 0027-8424 VL - 111 IS - 1 SP - 308 EP - 313 PB - National Acad. of Sciences CY - Washington ER - TY - JOUR A1 - Schulz, Tim Julius A1 - Thierbach, Renè A1 - Voigt, Anja A1 - Drewes, Gunnar A1 - Mietzner, Brun A1 - Steinberg, Pablo A1 - Pfeiffer, Andreas F. H. A1 - Ristow, Michael T1 - Induction of oxidative metabolism by mitochondrial frataxin inhibits cancer growth : Otto Warburg revisited N2 - 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 Y1 - 2006 UR - http://www.jbc.org/content/281/2/977.full.pdf+html U6 - https://doi.org/10.1074/jbc.M511064200 ER -