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HypoFlam SIGNED

Targeting hypothalamic inflammation in obesity and diabetes

Total Cost €

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EC-Contrib. €

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Partnership

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 HypoFlam project word cloud

Explore the words cloud of the HypoFlam project. It provides you a very rough idea of what is the project "HypoFlam" about.

primary    efforts    syndrome    discovered    ultimately    therapeutic    educational    implicates    pathogenesis    alarming    observe    humans    signalling    time    arcuate    disrupt    body    astrocytosis    diets    appetite    attempt    cell    responsible    systemic    functional    afferent    critical    array    diabetes    inflammation    rats    triggered    building    pathophysiology    pathologies    centers    efficient    transformative    diet    located    first    sensing    technologies    impaired    impair    metabolic    safe    fat    serve    intense    consumption    hypothesize    hormone    despite    biomedical    stages    appear    therapies    environments    incapacitate    nuclei    hypothalami    weight    plays    medical    cns    sugar    signals    inflammatory    preliminary    obesity    decline    arc    neuronal    breakthroughs    hfhs    incomplete    rate    hypothalamic    hypercaloric    pathogenic    regulatory    considerable    worldwide    reactive    regulating    glial    data    political    mice    microgliosis    diseases    homeostasis    nucleus    metabolism   

Project "HypoFlam" data sheet

The following table provides information about the project.

Coordinator
HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH 

Organization address
address: INGOLSTADTER LANDSTRASSE 1
city: NEUHERBERG
postcode: 85764
website: www.helmholtz-muenchen.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 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

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH DE (NEUHERBERG) coordinator 2˙402˙280.00

Map

 Project objective

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.

 Publications

year authors and title journal last update
List of publications.
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 García-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 García-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 García-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 Hrabě 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 García 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 García-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 García-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 García-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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