Journal Club paper of the week
Recent Publications of IDO Scientists
Duodenal nutrient exclusion improves metabolic syndrome and stimulates villus hyperplasia. Habegger KM, Al-Massadi O, Heppner KM, Myronovych A, Holland J, Berger J, Yi CX, Gao Y, Lehti M, Ottaway N, Amburgy S, Raver C, Müller TD, Pfluger PT, Kohli R, Perez-Tilve D, Seeley RJ, Tschöp MH. Gut. 2013 Oct 9.
Brown fat in a protoendothermic mammal fuels eutherian evolution. Oelkrug R, Goetze N, Exner C, Lee Y, Ganjam GK, Kutschke M, Müller S, Stöhr S, Tschöp MH, Crichton PG, Heldmaier G, Jastroch M, Meyer CW. Nat Commun. 2013;4:2140.
The orphan receptor Gpr83 regulates systemic energy metabolism via ghrelin-dependent and ghrelin-independent mechanisms. Müller TD, Müller A, Yi CX, Habegger KM, Meyer CW, Gaylinn BD, Finan B, Heppner K, Trivedi C, Bielohuby M, Abplanalp W, Meyer F, Piechowski CL, Pratzka J, Stemmer K, Holland J, Hembree J, Bhardwaj N, Raver C, Ottaway N, Krishna R, Sah R, Sallee FR, Woods SC, Perez-Tilve D, Bidlingmaier M, Thorner MO, Krude H, Smiley D, DiMarchi R, Hofmann S, Pfluger PT, Kleinau G, Biebermann H, Tschöp MH. Nat Commun. 2013;4:1968.
p62 links β-adrenergic input to mitochondrial function and thermogenesis. Müller TD, Lee SJ, Jastroch M, Kabra D, Stemmer K, Aichler M, Abplanalp B, Ananthakrishnan G, Bhardwaj N, Collins S, Divanovic S, Endele M, Finan B, Gao Y, Habegger KM, Hembree J, Heppner KM, Hofmann S, Holland J, Küchler D, Kutschke M, Krishna R, Lehti M, Oelkrug R, Ottaway N, Perez-Tilve D, Raver C, Walch AK, Schriever SC, Speakman J, Tseng YH, Diaz-Meco M, Pfluger PT, Moscat J, Tschöp MH. J Clin Invest. 2013 Jan 2;123(1):469-78.
Leptin regulation of Hsp60 impacts hypothalamic insulin signaling. Kleinridders A, Lauritzen HP, Ussar S, Christensen JH, Mori MA, Bross P, Kahn CR. J Clin Invest. 2013 Oct 1.
Insights into negative regulation by the glucocorticoid receptor from genome-wide profiling of inflammatory cistromes. Uhlenhaut NH, Barish GD, Yu RT, Downes M, Karunasiri M, Liddle C, Schwalie P, Hübner N, Evans RM. Mol Cell. 2013 Jan 10;49(1):158-71.
Targeted estrogen delivery reverses the metabolic syndrome. Finan B, Yang B, Ottaway N, Stemmer K, Müller TD, Yi CX, Habegger K, Schriever SC, García-Cáceres C, Kabra DG, Hembree J, Holland J, Raver C, Seeley RJ, Hans W, Irmler M, Beckers J, de Angelis MH, Tiano JP, Mauvais-Jarvis F, Perez-Tilve D, Pfluger P, Zhang L, Gelfanov V, DiMarchi RD, Tschöp MH. Nat Med. 2012 Dec;18(12):1847-56.
Sirtuin 1 and sirtuin 3: physiological modulators of metabolism. Nogueiras R, Habegger KM, Chaudhary N, Finan B, Banks AS, Dietrich MO, Horvath TL, Sinclair DA, Pfluger PT, Tschöp MH. Physiol Rev. 2012 Jul;92(3):1479-514.
Challenges and opportunities of defining clinical leptin resistance. Myers MG Jr, Heymsfield SB, Haft C, Kahn BB, Laughlin M, Leibel RL, Tschöp MH, Yanovski JA. Cell Metab. 2012 Feb 8;15(2):150-6.
Obesity is associated with hypothalamic injury in rodents and humans. Thaler JP, Yi CX, Schur EA, Guyenet SJ, Hwang BH, Dietrich MO, Zhao X, Sarruf DA, Izgur V, Maravilla KR, Nguyen HT, Fischer JD, Matsen ME, Wisse BE, Morton GJ, Horvath TL, Baskin DG, Tschöp MH, Schwartz MW. J Clin Invest. 2012 Jan 3;122(1):153-62.
Receptor antibodies as novel therapeutics for diabetes. Ussar S, Vienberg SG, Kahn CR. Sci Transl Med. 2011 Dec 14;3(113):113ps47.
Leptin regulates glutamate and glucose transporters in hypothalamic astrocytes. Fuente-Martín E, García-Cáceres C, Granado M, de Ceballos ML, Sánchez-Garrido MÁ, Sarman B, Liu ZW, Dietrich MO, Tena-Sempere M, Argente-Arizón P, Díaz F, Argente J, Horvath TL, Chowen JA. J Clin Invest. 2012 Nov 1;122(11):3900-13.
A genomic regulatory element that directs assembly and function of immune-specific AP-1-IRF complexes. Glasmacher E, Agrawal S, Chang AB, Murphy TL, Zeng W, Vander Lugt B, Khan AA, Ciofani M, Spooner CJ, Rutz S, Hackney J, Nurieva R, Escalante CR, Ouyang W, Littman DR, Murphy KM, Singh H. Science. 2012 Nov 16;338(6109):975-80.
Compensatory dendritic cell development mediated by BATF-IRF interactions. Tussiwand R, Lee WL, Murphy TL, Mashayekhi M, Wumesh KC, Albring JC, Satpathy AT, Rotondo JA, Edelson BT, Kretzer NM, Wu X, Weiss LA, Glasmacher E, Li P, Liao W, Behnke M, Lam SS, Aurthur CT, Leonard WJ, Singh H, Stallings CL, Sibley LD, Schreiber RD, Murphy KM. Nature. 2012 Oct 25;490(7421):502-7.
Scientific Advisory Board (SAB)
- Jeffrey Friedmann (Chair)
- Richard DiMarchi (Co-Chair)
- Martin Myers
- Randy Seeley
- Jorge Moscat
- Stephen O'Rahilly
- Rudolph Zechner
- Philipp Scherer
- Tamas Horvath
Helmholtz Alliance: ICEMED
Imaging and Curing Environmental Metabolic Diseases
The Helmholtz Alliance ICEMED is a network of complementary research excellence representing a worldwide unique research consortium of biomedical research scientists, clinicians and cutting edge metabolic imaging experts in Germany. ICEMED consists of more than 30 leading German diabetes and obesity research teams and research centers enhanced by cooperative alliances with Sanofi Aventis Pharmaceuticals and leading international diabetes and obesity research centers at Cambridge and Yale University.
The overarching intent of this alliance is to embrace the sustainable theme of finding new medicines to prevent and cure obesity and type 2 Diabetes over the next five years. The alliance will focus on identifying, visualizing, dissecting and targeting neural pathways (in both central control circuits and brain-periphery crosstalk) that regulate systems metabolism. This aspect of the alliance is synergistically enhanced by the integration of comprehensive neuroimaging expertise using cutting edge, in vivo metabolic imaging techniques like magnetic resonance imaging (MRI) and positron emission tomography (PET) in animal models and humans.
ICEMED connects multi-disciplinary basic research with clinical application toward personalized medicine.
The alliance is headed by the principal coordinator Prof Matthias Tschöp (Munich) and Prof Jon Shah (Jülich).
In accord with the Helmholtz mission to generate “solutions for the grand challenges of our society”, outstanding researchers from four Helmholtz Centers in Germany collaborate with leading basic, translational, clinical and imaging experts under the umbrella of the Helmholtz Alliance called ICEMED to find answers to one of the most important biomedical research challenges of our time, obesity and Type 2 Diabetes (T2DM).
The overarching intent of ICEMED is to embrace the sustainable theme of unveiling new targets and finding new medicines to prevent and cure obesity and T2DM. This endeavor connects multi-disciplinary basic research with clinical application toward personalized medicine through the use of cutting edge technology. Specifically, ICEMED will be enhanced through the application of state-of-the-art in vivo metabolic imaging. The Alliance will apply unprecedentedly sophisticated levels of magnetic resonance imaging and positron emission tomography in animal models and humans to the field of obesity and T2DM. The integrated effort of this collaborative Alliance of more than 30 successful research teams will focus effectively on identifying, visualizing, dissecting, and targeting neural pathways in key control processes of central circuits and in brain-periphery cross-talk that regulate systems metabolism.
This Alliance will build upon the outstanding international expertise and strengths in the area of obesity, diabetes and neuroscience research already existing in Germany. Central components of this Alliance include state-of-the art cell based signaling research, cutting edge targeted mouse mutagenesis and phenotyping, as well as unique diabetes and obesity patient cohorts along with advanced pre-clinical and clinical pharmacology expertise. The consortium includes the leading German diabetes and obesity scientists and research centers enhanced by cooperative alliance with Sanofi Aventis Pharmaceuticals and leading international diabetes and obesity research centers at Cambridge (UK) and Yale University (USA).
This structure will be synergistically enhanced by the integration of comprehensive neuroimaging expertise along with worldwide unique instruments for metabolic imaging located at the Helmholtz Forschungszentrum Jülich. Unprecedented advances toward metabolic imaging will be made by the use of the hybrid MR-PET instruments. Currently, the Forschungszentrum Jülich has the world’s only 9.4T MRPET machine capable of human imaging allowing for the first time the simultaneous measurement of glucose metabolism with either the rate of cerebral oxygen consumption or the turnover of ATP/ADP. This unique combination of expertise and infrastructure enables the resulting ICEMED Alliance to tackle one of today’s most important and urgent health problems. Focusing on the central control of metabolism and metabolic disease, ICEMED has established clear and sustainable goals centered on control by the Central Nervous System (CNS).
The rationale is that the CNS is the integration center, modulating and orchestrating all systemic metabolic processes via constant organ cross talk and at the same time represents the key target of environmental triggers for metabolic diseases such as hyper-caloric diets and stress. To this end, a concerted effort utilizing human genetics, functional genomics, protein biochemistry, physiology, medicinal chemistry, stem cell biology, neuroimaging, advanced targeted mouse mutagenesis, advanced neuropharmacology and holistic phenotype analysis will be combined with cutting edge human physiology and clinical research in order to create an unprecedented and translationally-meaningful blueprint for the molecular-systemic control of energy, lipid and glucose metabolism in health and disease. This comprehensive program will be further enhanced by strategic integration of experienced industry partners (Sanofi Aventis Diabetes and Obesity Franchise, Frankfurt, Germany) and leading international research centers (Prof. O’Rahilly, Univ. of Cambridge, UK; Prof Horvath, Yale Medical School, USA).
ICEMED will generate significant opportunities to contribute to the molecular and pathophysiological understanding of the current pandemic of diabetes and obesity, allowing for the development of potent therapeutics with the potential to reverse and hopefully stop the pandemic trend. The research focus on central control of environmentally-induced pathologies of systems metabolism offers flexible growth opportunities for the Alliance in several future directions based on emerging findings.