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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.

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

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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