Explore the words cloud of the HypoFlam project. It provides you a very rough idea of what is the project "HypoFlam" about.
The following table provides information about the project.
Coordinator |
HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Organization address contact info |
Coordinator Country | Germany [DE] |
Total cost | 2˙402˙280 € |
EC max contribution | 2˙402˙280 € (100%) |
Programme |
1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC)) |
Code Call | ERC-2015-AdG |
Funding Scheme | ERC-ADG |
Starting year | 2016 |
Duration (year-month-day) | from 2016-09-01 to 2021-08-31 |
Take a look of project's partnership.
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1 | HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH | DE (NEUHERBERG) | coordinator | 2˙402˙280.00 |
Despite educational, political and biomedical research efforts, obesity, type 2 diabetes and related metabolic diseases are increasing worldwide at an alarming rate. Failure to deliver efficient and safe medical therapies is a result of our incomplete understanding of the pathogenesis of the metabolic syndrome. Current knowledge implicates impaired CNS control over appetite, body weight and systemic metabolism as a key pathogenic process leading to obesity and type 2 diabetes. Yet, years of intense study focused on neuronal signalling have produced no transformative breakthroughs. Control centers located in the hypothalamic arcuate nucleus (ARC) serve as primary targets of afferent hormone signals regulating systemic control of body weight and metabolism and appear to be most affected by high fat high sugar (HFHS) diets. Recently, we discovered that in the early stages of the metabolic syndrome induced by consumption of a HFHS diet, significant changes beyond neuronal pathologies occur in hypothalamic nuclei responsible for metabolic control, such as the ARC. Specifically, we observe in hypothalami of mice, rats and humans increased reactive microgliosis and astrocytosis as well as a decline in regulatory T-cell presence. We hypothesize that hypothalamic inflammatory processes triggered by hypercaloric environments impair hormone sensing, disrupt glial homeostasis and incapacitate these hypothalamic control centers, ultimately contributing to development of obesity and diabetes. Building on a considerable body of preliminary data, we will apply an array of advanced technologies to A) develop a functional understanding of the pathophysiology of diet-induced hypothalamic inflammation, B) test if hypothalamic inflammation plays a critical role in the development of the metabolic syndrome, and C) attempt to target these novel pathogenic processes for the first time using novel targeted therapeutic approaches.
year | authors and title | journal | last update |
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2019 |
Léa Décarie-Spain, Alexandre Fisette, Zhimeng Zhu, Bin Yang, Richard D. DiMarchi, Matthias H. Tschöp, Brian Finan, Stephanie Fulton, Christoffer Clemmensen GLP-1/dexamethasone inhibits food reward without inducing mood and memory deficits in mice published pages: 55-63, ISSN: 0028-3908, DOI: 10.1016/j.neuropharm.2019.03.035 |
Neuropharmacology 151 | 2019-10-29 |
2018 |
Sara J. Brandt, Anna Götz, Matthias H. Tschöp, Timo D. Müller Gut hormone polyagonists for the treatment of type 2 diabetes published pages: 190-201, ISSN: 0196-9781, DOI: 10.1016/j.peptides.2017.12.021 |
Peptides 100 | 2019-06-13 |
2017 |
Chun-Xia Yi, Marc Walter, Yuanqing Gao, Soledad Pitra, Beata Legutko, Stefanie Kälin, Clarita Layritz, Cristina GarcÃa-Cáceres, Maximilian Bielohuby, Martin Bidlingmaier, Stephen C. Woods, Alexander Ghanem, Karl-Klaus Conzelmann, Javier E. Stern, Martin Jastroch, Matthias H. Tschöp TNFα drives mitochondrial stress in POMC neurons in obesity published pages: 15143, ISSN: 2041-1723, DOI: 10.1038/ncomms15143 |
Nature Communications 8 | 2019-06-13 |
2017 |
Luis Varela, Shigetomo Suyama, Yan Huang, Marya Shanabrough, Matthias H. Tschöp, Xiao-Bing Gao, Frank J. Giordano, Tamas L. Horvath Endothelial HIF-1α Enables Hypothalamic Glucose Uptake to Drive POMC Neurons published pages: 1511-1520, ISSN: 0012-1797, DOI: 10.2337/db16-1106 |
Diabetes 66/6 | 2019-06-13 |
2017 |
Gustav Colldén, Matthias Tschöp, Timo Müller Therapeutic Potential of Targeting the Ghrelin Pathway published pages: 798, ISSN: 1422-0067, DOI: 10.3390/ijms18040798 |
International Journal of Molecular Sciences 18/4 | 2019-06-13 |
2017 |
Christoffer Clemmensen, Timo D. Müller, Stephen C. Woods, Hans-Rudolf Berthoud, Randy J. Seeley, Matthias H. Tschöp Gut-Brain Cross-Talk in Metabolic Control published pages: 758-774, ISSN: 0092-8674, DOI: 10.1016/j.cell.2017.01.025 |
Cell 168/5 | 2019-06-13 |
2017 |
Yuanqing Gao, Maximilian Bielohuby, Thomas Fleming, Gernot F. Grabner, Ewout Foppen, Wagner Bernhard, Mara Guzmán-Ruiz, Clarita Layritz, Beata Legutko, Erwin Zinser, Cristina GarcÃa-Cáceres, Ruud M. Buijs, Stephen C. Woods, Andries Kalsbeek, Randy J. Seeley, Peter P. Nawroth, Martin Bidlingmaier, Matthias H. Tschöp, Chun-Xia Yi Dietary sugars, not lipids, drive hypothalamic inflammation published pages: 897-908, ISSN: 2212-8778, DOI: 10.1016/j.molmet.2017.06.008 |
Molecular Metabolism 6/8 | 2019-06-13 |
2018 |
S J Brandt, M Kleinert, M H Tschöp, T D Müller Are peptide conjugates the golden therapy against obesity? published pages: R109-R119, ISSN: 0022-0795, DOI: 10.1530/joe-18-0264 |
Journal of Endocrinology 238/2 | 2019-06-13 |
2017 |
Yuanqing Gao, Clarita Layritz, Beata Legutko, Thomas O. Eichmann, Elise Laperrousaz, Valentine S. Moullé, Celine Cruciani-Guglielmacci, Christophe Magnan, Serge Luquet, Stephen C. Woods, Robert H. Eckel, Chun-Xia Yi, Cristina Garcia-Caceres, Matthias H. Tschöp Disruption of Lipid Uptake in Astroglia Exacerbates Diet-Induced Obesity published pages: 2555-2563, ISSN: 0012-1797, DOI: 10.2337/db16-1278 |
Diabetes 66/10 | 2019-06-13 |
2017 |
Katrin Fischer, Henry H Ruiz, Kevin Jhun, Brian Finan, Douglas J Oberlin, Verena van der Heide, Anastasia V Kalinovich, Natasa Petrovic, Yochai Wolf, Christoffer Clemmensen, Andrew C Shin, Senad Divanovic, Frank Brombacher, Elke Glasmacher, Susanne Keipert, Martin Jastroch, Joachim Nagler, Karl-Werner Schramm, Dasa Medrikova, Gustav Collden, Stephen C Woods, Stephan Herzig, Dirk Homann, Steffen Jung, Jan Nedergaard, Barbara Cannon, Matthias H Tschöp, Timo D Müller, Christoph Buettner Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis published pages: 623-630, ISSN: 1078-8956, DOI: 10.1038/nm.4316 |
Nature Medicine 23/5 | 2019-06-13 |
2017 |
Maximilian Kleinert, Christoffer Clemmensen, Kerstin Stemmer, Timo D. Müller, Richard D. DiMarchi, Matthias H. Tschöp Emerging Poly-Agonists for Obesity and Type 2 Diabetes published pages: 1647-1649, ISSN: 1930-7381, DOI: 10.1002/oby.21932 |
Obesity 25/10 | 2019-06-13 |
2018 |
Anne-Laure Poher, Matthias H. Tschöp, Timo D. Müller Ghrelin regulation of glucose metabolism published pages: 236-242, ISSN: 0196-9781, DOI: 10.1016/j.peptides.2017.12.015 |
Peptides 100 | 2019-06-13 |
2017 |
Carmelo Quarta, Christoffer Clemmensen, Zhimeng Zhu, Bin Yang, Sini S. Joseph, Dominik Lutter, Chun-Xia Yi, Elisabeth Graf, Cristina GarcÃa-Cáceres, Beata Legutko, Katrin Fischer, Robert Brommage, Philippe Zizzari, Bernardo S. Franklin, Martin Krueger, Marco Koch, Sabine Vettorazzi, Pengyun Li, Susanna M. Hofmann, Mostafa Bakhti, Aimée Bastidas-Ponce, Heiko Lickert, Tim M. Strom, Valerie Gailus-Durner, Ingo Bechmann, Diego Perez-Tilve, Jan Tuckermann, Martin HrabÄ› de Angelis, Darleen Sandoval, Daniela Cota, Eicke Latz, Randy J. Seeley, Timo D. Müller, Richard D. DiMarchi, Brian Finan, Matthias H. Tschöp Molecular Integration of Incretin and Glucocorticoid Action Reverses Immunometabolic Dysfunction and Obesity published pages: 620-632.e6, ISSN: 1550-4131, DOI: 10.1016/j.cmet.2017.08.023 |
Cell Metabolism 26/4 | 2019-06-13 |
2018 |
Lisa Suwandhi, Simone Hausmann, Alexander Braun, Tim Gruber, Silke S. Heinzmann, Eric J.C. Gálvez, Achim Buck, Beata Legutko, Andreas Israel, Annette Feuchtinger, Elizabeth Haythorne, Harald Staiger, Martin Heni, Hans-Ulrich Häring, Philippe Schmitt-Kopplin, Axel Walch, Cristina GarcÃa Cáceres, Matthias H. Tschöp, Guy A. Rutter, Till Strowig, Martin Elsner, Siegfried Ussar Chronic d-serine supplementation impairs insulin secretion published pages: 191-202, ISSN: 2212-8778, DOI: 10.1016/j.molmet.2018.07.002 |
Molecular Metabolism 16 | 2019-05-22 |
2019 |
Carmelo Quarta, Alexandre Fisette, Yanjun Xu, Gustav Colldén, Beata Legutko, Yu-Ting Tseng, Alexander Reim, Michael Wierer, Maria Caterina De Rosa, Valentina Klaus, Rick Rausch, Vidhu V. Thaker, Elisabeth Graf, Tim M. Strom, Anne-Laure Poher, Tim Gruber, Ophélia Le Thuc, Alberto Cebrian-Serrano, Dhiraj Kabra, Luigi Bellocchio, Stephen C. Woods, Gert O. Pflugfelder, Rubén Nogueiras, Lori Zeltser, Ilona C. Grunwald Kadow, Anne Moon, Cristina GarcÃa-Cáceres, Matthias Mann, Mathias Treier, Claudia A. Doege, Matthias H. Tschöp Functional identity of hypothalamic melanocortin neurons depends on Tbx3 published pages: 222-235, ISSN: 2522-5812, DOI: 10.1038/s42255-018-0028-1 |
Nature Metabolism 1/2 | 2019-05-22 |
2019 |
Cristina GarcÃa-Cáceres, Eglantine Balland, Vincent Prevot, Serge Luquet, Stephen C. Woods, Marco Koch, Tamas L. Horvath, Chun-Xia Yi, Julia A. Chowen, Alexei Verkhratsky, Alfonso Araque, Ingo Bechmann, Matthias H. Tschöp Role of astrocytes, microglia, and tanycytes in brain control of systemic metabolism published pages: 7-14, ISSN: 1097-6256, DOI: 10.1038/s41593-018-0286-y |
Nature Neuroscience 22/1 | 2019-05-22 |
2019 |
Christoffer Clemmensen, Brian Finan, Timo D. Müller, Richard D. DiMarchi, Matthias H. Tschöp, Susanna M. Hofmann Emerging hormonal-based combination pharmacotherapies for the treatment of metabolic diseases published pages: 90-104, ISSN: 1759-5029, DOI: 10.1038/s41574-018-0118-x |
Nature Reviews Endocrinology 15/2 | 2019-05-22 |
2018 |
T. D. Müller, C. Clemmensen, B. Finan, R. D. DiMarchi, M. H. Tschöp Anti-Obesity Therapy: from Rainbow Pills to Polyagonists published pages: 712-746, ISSN: 0031-6997, DOI: 10.1124/pr.117.014803 |
Pharmacological Reviews 70/4 | 2019-05-22 |
2018 |
S. J. Brandt, T. D. Müller, R. D. DiMarchi, M. H. Tschöp, K. Stemmer Peptide-based multi-agonists: a new paradigm in metabolic pharmacology published pages: 581-602, ISSN: 0954-6820, DOI: 10.1111/joim.12837 |
Journal of Internal Medicine 284/6 | 2019-05-22 |
2016 |
Cristina GarcÃa-Cáceres, Carmelo Quarta, Luis Varela, Yuanqing Gao, Tim Gruber, Beata Legutko, Martin Jastroch, Pia Johansson, Jovica Ninkovic, Chun-Xia Yi, Ophelia Le Thuc, Klara Szigeti-Buck, Weikang Cai, Carola W. Meyer, Paul T. Pfluger, Ana M. Fernandez, Serge Luquet, Stephen C. Woods, Ignacio Torres-Alemán, C. Ronald Kahn, Magdalena Götz, Tamas L. Horvath, Matthias H. Tschöp Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability published pages: 867-880, ISSN: 0092-8674, DOI: 10.1016/j.cell.2016.07.028 |
Cell 166/4 | 2019-06-06 |
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