TY - GEN A1 - Volckmar, Anna-Lena A1 - Han, Chung-Ting A1 - Pütter, Carolin A1 - Haas, Stefan A1 - Vogel, Carla I. G. A1 - Knoll, Nadja A1 - Struve, Christoph A1 - Göbel, Maria A1 - Haas, Katharina A1 - Herrfurth, Nikolas A1 - Jarick, Ivonne A1 - Grallert, Harald A1 - Schürmann, Annette A1 - Al- Hasani, Hadi A1 - Hebebrand, Johannes A1 - Sauer, Sascha A1 - Hinney, Anke T1 - Analysis of genes involved in body weight regulation by targeted re-sequencing T2 - PLoS ONE N2 - Introduction Genes involved in body weight regulation that were previously investigated in genome-wide association studies (GWAS) and in animal models were target-enriched followed by massive parallel next generation sequencing. Methods We enriched and re-sequenced continuous genomic regions comprising FTO, MC4R, TMEM18, SDCCAG8, TKNS, MSRA and TBC1D1 in a screening sample of 196 extremely obese children and adolescents with age and sex specific body mass index (BMI) >= 99th percentile and 176 lean adults (BMI <= 15th percentile). 22 variants were confirmed by Sanger sequencing. Genotyping was performed in up to 705 independent obesity trios (extremely obese child and both parents), 243 extremely obese cases and 261 lean adults. Results and Conclusion We detected 20 different non-synonymous variants, one frame shift and one nonsense mutation in the 7 continuous genomic regions in study groups of different weight extremes. For SNP Arg695Cys (rs58983546) in TBC1D1 we detected nominal association with obesity (p(TDT) = 0.03 in 705 trios). Eleven of the variants were rare, thus were only detected heterozygously in up to ten individual(s) of the complete screening sample of 372 individuals. Two of them (in FTO and MSRA) were found in lean individuals, nine in extremely obese. In silico analyses of the 11 variants did not reveal functional implications for the mutations. Concordant with our hypothesis we detected a rare variant that potentially leads to loss of FTO function in a lean individual. For TBC1D1, in contrary to our hypothesis, the loss of function variant (Arg443Stop) was found in an obese individual. Functional in vitro studies are warranted. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 423 KW - melanocortin-4 receptor gene KW - stimulated glucose-uptake KW - life-style intervention KW - onset extreme obesity KW - genome-wide analysis KW - mass index KW - FTO gene KW - fat mass KW - overweight children KW - diabetes-melllitus Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-410289 ER - TY - JOUR A1 - Engeli, Stefan A1 - Lehmann, Anne-Christin A1 - Kaminski, Jana A1 - Haas, Verena A1 - Janke, Urgen A1 - Janke, Jürgen A1 - Zoerner, Alexander A. A1 - Luft, Friedrich C. A1 - Tsikas, Dimitrios A1 - Jordan, Jens T1 - Influence of dietary fat intake on the endocannabinoid system in lean and obese subjects JF - Obesity N2 - Objective: Endocannabinoid system (ECS) activation promotes obesity-associated metabolic disease. Increased dietary fat intake increases blood endocannabinoids and alters adipose and skeletal muscle ECS gene expression in human. Methods: Two weeks isocaloric low- (LFD) and high-fat diets (HFD) in obese (n = 12) and normal- weight (n = 17) subjects in a randomized cross-over study were compared. Blood endocannabinoids were measured in the fasting condition and after food intake using mass spectrometry. Adipose and skeletal muscle gene expression was determined using real-time RT-PCR. Results: Baseline fasting plasma endocannabinoids were similar with both diets. Anandamide decreased similarly with high- or low-fat test meals in both groups. Baseline arachidonoylglycerol plasma concentrations were similar between groups and diets, and unresponsive to eating. In subcutaneous adipose tissue, DAGL-alpha mRNA was upregulated and fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) mRNAs were down-regulated in obese subjects, but the diets had no influence. In contrast, the HFD produced pronounced reductions in skeletal muscle CB1-R and MAGL mRNA expression, whereas obesity did not affect muscular gene expression. Conclusions: Weight-neutral changes in dietary fat intake cannot explain excessive endocannabinoid availability in human obesity. Obesity and dietary fat intake affect ECS gene expression in a tissue-specific manner. Y1 - 2014 U6 - https://doi.org/10.1002/oby.20728 SN - 1930-7381 SN - 1930-739X VL - 22 IS - 5 SP - E70 EP - E76 PB - Wiley-Blackwell CY - Hoboken ER - TY - JOUR A1 - Kottmeier, Christoph A1 - Agnon, Amotz A1 - Al-Halbouni, Djamil A1 - Alpert, Pinhas A1 - Corsmeier, Ulrich A1 - Dahm, Torsten A1 - Eshel, Adam A1 - Geyer, Stefan A1 - Haas, Michael A1 - Holohan, Eoghan A1 - Kalthoff, Norbert A1 - Kishcha, Pavel A1 - Krawczyk, Charlotte A1 - Lati, Joseph A1 - Laronne, Jonathan B. A1 - Lott, Friederike A1 - Mallast, Ulf A1 - Merz, Ralf A1 - Metzger, Jutta A1 - Mohsen, Ayman A1 - Morin, Efrat A1 - Nied, Manuela A1 - Roediger, Tino A1 - Salameh, Elias A1 - Sawarieh, Ali A1 - Shannak, Benbella A1 - Siebert, Christian A1 - Weber, Michael T1 - New perspectives on interdisciplinary earth science at the Dead Sea: The DESERVE project JF - The science of the total environment : an international journal for scientific research into the environment and its relationship with man N2 - The Dead Sea region has faced substantial environmental challenges in recent decades, including water resource scarcity, similar to 1 m annual decreases in the water level, sinkhole development, ascending-brine freshwater pollution, and seismic disturbance risks. Natural processes are significantly affected by human interference as well as by climate change and tectonic developments over the long term. To get a deep understanding of processes and their interactions, innovative scientific approaches that integrate disciplinary research and education are required. The research project DESERVE (Helmholtz Virtual Institute Dead Sea Research Venue) addresses these challenges in an interdisciplinary approach that includes geophysics, hydrology, and meteorology. The project is implemented by a consortium of scientific institutions in neighboring countries of the Dead Sea (Israel, Jordan, Palestine Territories) and participating German Helmholtz Centres (KIT, GFZ, UFZ). A new monitoring network of meteorological, hydrological, and seismic/geodynamic stations has been established, and extensive field research and numerical simulations have been undertaken. For the first time, innovative measurement and modeling techniques have been applied to the extreme conditions of the Dead Sea and its surroundings. The preliminary results show the potential of these methods. First time ever performed eddy covariance measurements give insight into the governing factors of Dead Sea evaporation. High-resolution bathymetric investigations reveal a strong correlation between submarine springs and neo-tectonic patterns. Based on detailed studies of stratigraphy and borehole information, the extension of the subsurface drainage basin of the Dead Sea is now reliably estimated. Originality has been achieved in monitoring flash floods in an arid basin at its outlet and simultaneously in tributaries, supplemented by spatio-temporal rainfall data. Low-altitude, high resolution photogrammetry, allied to satellite image analysis and to geophysical surveys (e.g. shear-wave reflections) has enabled a more detailed characterization of sinkhole morphology and temporal development and the possible subsurface controls thereon. All the above listed efforts and scientific results take place with the interdisciplinary education of young scientists. They are invited to attend joint thematic workshops and winter schools as well as to participate in field experiments. (C) 2015 The Authors. Published by Elsevier B.V. KW - Climate KW - Water balance KW - Flash floods KW - Seismicity KW - Sinkholes KW - Education Y1 - 2016 U6 - https://doi.org/10.1016/j.scitotenv.2015.12.003 SN - 0048-9697 SN - 1879-1026 VL - 544 SP - 1045 EP - 1058 PB - Elsevier CY - Amsterdam ER -