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Prof. Johan Auwerx, 2009 Awardee
Some foods do more than just nourish our body; they also communicate with our cells, giving orders, for instance, to shed fat from adipose tissue, in similar fashion to certain hormones. This communication system, hitherto unknown, was revealed by Professor Johan Auwerx, thereby opening the way for new preventive and therapeutic strategies to combat obesity and cardiometabolic diseases such as type 2 diabetes and hypertension. The discovery earned him the prestigious Danone International Prize for Nutrition worth 120,000 Euros. Please click on the links below to find out more about Prof. Auwerx´s work: RESEARCH WORK SELECTED BIBLIOGRAPHY CV Research Work
The underlying hypothesis of his research is that the nutrients in our diet have a direct influence on transcription. More precisely, the studies by Johan Auwerx focus on the mechanism of shedding of fat from adipose tissue, thereby paving the way for new preventive and therapeutic strategies to combat obesity and cardiometabolic diseases such as type 2 diabetes and hypertension. “We have discovered for instance that certain fatty acids activate specific nuclear receptors within the cells of our body known as PPARs (peroxisome proliferator-activated receptors),” continued the research scientist. “The latter play a major role in fat metabolism and thus offer a new approach to the treatment of insulin resistance and the metabolic syndrome.”
Studies published in Nature and Cell Metabolism Prof. Johan Auwerx is the author of numerous publications in internationally renowned journals, including Nature and Cell Metabolism. His studies have investigated certain transcription factors (e.g. nuclear factors such as PPARs) and transcription co-factors (e.g. sirtuins or SIRT) that act as "molecular traps" for nutrients and intracellular metabolites. These proteins in fact play a dual role: they detect changes in concentrations of certain nutrients or metabolites in the environment and they react to this information by modifying transcription of the genes involved in metabolic control, thereby ensuring a suitable response. In a recent issue of Nature in April 2009 [1], he describes the mechanisms by which transcription factors and co-factors allow the body to "sense" an energy deficit following long periods without food or prolonged exercise, before allowing the body to use this information to stimulate the release or production of energy from fat tissue (see diagram). His team showed that AMPK (AMP-activated protein kinase), an enzyme sensitive to the ratio of ATP to AMP and involved in regulation in cellular energy status, controls gene expression involved in energy metabolism by stimulating another metabolic regulator, sirtuin SIRT1 (diagrams from the issue of Nature appended). The function of this enzyme is to activate the nuclear receptor PPAR PGC-1á (peroxisome proliferator-activated receptor-gamma co-activator 1 alpha) as well as two Forkhead-type FOXO transcription factors. A few months earlier Prof. Auwerx' team had demonstrated the role of these agents in fatty acid metabolism. This discovery accounts for the numerous similar effects of AMPK and SIRT1 regarding energy metabolism: they enhance metabolic reactions that generate ATP (oxidation of fatty acids and carbohydrates) and reduce biochemical reactions that consume ATP (e.g. lipogenesis). Specific activation of SIRT1 could thus stimulate fatty acid metabolism by mimicking energy demand, thereby protecting against obesity. Prof. Auwerx and his co-workers showed the ability of certain foods such as resveratrol to specifically activate SIRT1. Other studies involving a synthetic substance were published in Cell Metabolism. This molecule, obtained by Prof. Auwerx and his team, noticeably improved endurance in animals and provided considerable protection against obesity and diet-induced insulin resistance by increasing oxidative metabolism in skeletal muscle, liver and brown adipose tissue. These studies provide an understanding of how to stimulate breakdown of fatty acids stored within the body, thereby preventing obesity and associated cardiometabolic risk. Selected Bibliography
1. R Saladin, P De Vos, M Guerre-Millo, A Leturque, J Girard, B Staels, and J Auwerx. Transient increase in obese gene expression after food intake or insulin administration.. In Nature, volume 377, number 6549, pages 527-9, 1995.
2. N Vu-Dac, K Schoonjans, V Kosykh, J Dallongeville, J C Fruchart, B Staels, and J Auwerx. Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor.. In The Journal of clinical investigation, volume 96, number 2, pages 741-50, 1995. 3. T Lemberger, R Saladin, M Vázquez, F Assimacopoulos, B Staels, B Desvergne, W Wahli, and J Auwerx. Expression of the peroxisome proliferator-activated receptor alpha gene is stimulated by stress and follows a diurnal rhythm.. In The Journal of biological chemistry, volume 271, number 3, pages 1764-9, 1996. 4. P De Vos, A M Lefebvre, S G Miller, M Guerre-Millo, K Wong, R Saladin, L G Hamann, B Staels, M R Briggs, and J Auwerx. Thiazolidinediones repress ob gene expression in rodents via activation of peroxisome proliferator-activated receptor gamma.. In The Journal of clinical investigation, volume 98, number 4, pages 1004-9, 1996. 5. K Schoonjans, J Peinado-Onsurbe, A M Lefebvre, R A Heyman, M Briggs, S Deeb, B Staels, and J Auwerx. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene.. In The EMBO journal, volume 15, number 19, pages 5336-48, 1996. 6. L Fajas, D Auboeuf, E Raspé, K Schoonjans, A M Lefebvre, R Saladin, J Najib, M Laville, J C Fruchart, S Deeb, A Vidal-Puig, J Flier, M R Briggs, B Staels, H Vidal, and J Auwerx. The organization, promoter analysis, and expression of the human PPARgamma gene.. In The Journal of biological chemistry, volume 272, number 30, pages 18779-89, 1997. 7. A M Lefebvre, I Chen, P Desreumaux, J Najib, J C Fruchart, K Geboes, M Briggs, R Heyman, and J Auwerx. Activation of the peroxisome proliferator-activated receptor gamma promotes the development of colon tumors in C57BL/6J-APCMin/+ mice.. In Nature medicine, volume 4, number 9, pages 1053-7, 1998. 8. S S Deeb, L Fajas, M Nemoto, J Pihlajamäki, L Mykkänen, J Kuusisto, M Laakso, W Fujimoto, and J Auwerx. A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity.. In Nature genetics, volume 20, number 3, pages 284-7, 1998. 9. L Fajas, K Schoonjans, L Gelman, J B Kim, J Najib, G Martin, J C Fruchart, M Briggs, B M Spiegelman, and J Auwerx. Regulation of peroxisome proliferator-activated receptor gamma expression by adipocyte differentiation and determination factor 1/sterol regulatory element binding protein 1: implications for adipocyte differentiation and metabolism.. In Molecular and cellular biology, volume 19, number 8, pages 5495-503, 1999. 10. L Gelman, G Zhou, L Fajas, E Raspé, J C Fruchart, and J Auwerx. p300 interacts with the N- and C-terminal part of PPARgamma2 in a ligand-independent and -dependent manner, respectively.. In The Journal of biological chemistry, volume 274, number 12, pages 7681-8, 1999. 11. T T Lu, M Makishima, J J Repa, K Schoonjans, T A Kerr, J Auwerx, and D J Mangelsdorf. Molecular basis for feedback regulation of bile acid synthesis by nuclear receptors.. In Molecular cell, volume 6, number 3, pages 507-15, 2000. 12. T Claudel, M D Leibowitz, C Fiévet, A Tailleux, B Wagner, J J Repa, G Torpier, J M Lobaccaro, J R Paterniti, D J Mangelsdorf, R A Heyman, and J Auwerx. Reduction of atherosclerosis in apolipoprotein E knockout mice by activation of the retinoid X receptor.. In Proceedings of the National Academy of Sciences of the United States of America, volume 98, number 5, pages 2610-5, 2001. 13. J F Colombel, and J Auwerx. Attenuation of colon inflammation through activators of the retinoid X receptor (RXR)/peroxisome proliferator-activated receptor gamma (PPARgamma) heterodimer. A basis for new therapeutic strategies.. In The Journal of experimental medicine, volume 193, number 7, pages 827-38, 2001. 14. S Rocchi, F Picard, J Vamecq, L Gelman, N Potier, D Zeyer, L Dubuquoy, P Bac, M F Champy, K D Plunket, L M Leesnitzer, S G Blanchard, P Desreumaux, D Moras, J P Renaud, and J Auwerx. A unique PPARgamma ligand with potent insulin-sensitizing yet weak adipogenic activity.. In Molecular cell, volume 8, number 4, pages 737-47, 2001. 15.Lluis Fajas, Rebecca L Landsberg, Yolande Huss-Garcia, Claude Sardet, Jacqueline A Lees, and Johan Auwerx. E2Fs regulate adipocyte differentiation.. In Developmental cell, volume 3, number 1, pages 39-49, 2002. 16. Carole Brendel, Kristina Schoonjans, Oronza A Botrugno, Eckardt Treuter, and Johan Auwerx. The small heterodimer partner interacts with the liver X receptor alpha and represses its transcriptional activity.. In Molecular endocrinology (Baltimore, Md.), volume 16, number 9, pages 2065-76, 2002. 17. Lluis Fajas, Viviane Egler, Raphael Reiter, Jacob Hansen, Karsten Kristiansen, Marie-Bernard Debril, Stéphanie Miard, and Johan Auwerx. The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation.. In Developmental cell, volume 3, number 6, pages 903-10, 2002. 18. Frédéric Picard, Martine Géhin, Jean- Sébastien Annicotte, Stéphane Rocchi, Marie-France Champy, Bert W O'Malley, Pierre Chambon, and Johan Auwerx. SRC-1 and TIF2 control energy balance between white and brown adipose tissues.. In Cell, volume 111, number 7, pages 931-41, 2003. 19. Hana Koutnikova, Terrie-Anne Cock, Mitsuhiro Watanabe, Sander M Houten, Marie-France Champy, Andreé Dierich, and Johan Auwerx. Compensation by the muscle limits the metabolic consequences of lipodystrophy in PPAR gamma hypomorphic mice.. In Proceedings of the National Academy of Sciences of the United States of America, volume 100, number 24, pages 14457-62, 2003. 20. Jean-Sébastien Annicotte, Elisabeth Fayard, Galvin H Swift, Lars Selander, Helena Edlund, Toshiya Tanaka, Tatsuhiko Kodama, Kristina Schoonjans, and Johan Auwerx. Pancreatic-duodenal homeobox 1 regulates expression of liver receptor homolog 1 during pancreas development.. In Molecular and cellular biology, volume 23, number 19, pages 6713-24, 2003. 21. Lluis Fajas, Jean-Sébastien Annicotte, Stéphanie Miard, David Sarruf, Mitsuhiro Watanabe, and Johan Auwerx. Impaired pancreatic growth, beta cell mass, and beta cell function in E2F1 (-/- )mice.. In The Journal of clinical investigation, volume 113, number 9, pages 1288-95, 2004. 22. Mitsuhiro Watanabe, Sander M Houten, Li Wang, Antonio Moschetta, David J Mangelsdorf, Richard A Heyman, David D Moore, and Johan Auwerx. Bile acids lower triglyceride levels via a pathway involving FXR, SHP, and SREBP-1c.. In The Journal of clinical investigation, volume 113, number 10, pages 1408-18, 2004. 23. Oronza A Botrugno, Elisabeth Fayard, Jean-Sébastien Annicotte, Céline Haby, Thomas Brennan, Olivia Wendling, Toshiya Tanaka, Tatsuhiko Kodama, Winston Thomas, Johan Auwerx, and Kristina Schoonjans. Synergy between LRH-1 and beta-catenin induces G1 cyclin-mediated cell proliferation.. In Molecular cell, volume 15, number 4, pages 499-509, 2004. 24. Sung Hee Um, Francesca Frigerio, Mitsuhiro Watanabe, Frédéric Picard, Manel Joaquin, Melanie Sticker, Stefano Fumagalli, Peter R Allegrini, Sara C Kozma, Johan Auwerx, and George Thomas. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity.. In Nature, volume 431, number 7005, pages 200-5, 2004. 25. Kristina Schoonjans, Laurent Dubuquoy, Joseph Mebis, Elisabeth Fayard, Olivia Wendling, Céline Haby, Karel Geboes, and Johan Auwerx. Liver receptor homolog 1 contributes to intestinal tumor formation through effects on cell cycle and inflammation.. In Proceedings of the National Academy of Sciences of the United States of America, volume 102, number 6, pages 2058-62, 2005. 26. Carmen A Argmann, Pierre Chambon, and Johan Auwerx. Mouse phenogenomics: the fast track to "systems metabolism".. In Cell metabolism, volume 2, number 6, pages 349-60, 2005. 27. Mitsuhiro Watanabe, Sander M Houten, Chikage Mataki, Marcelo A Christoffolete, Brian W Kim, Hiroyuki Sato, Nadia Messaddeq, John W Harney, Osamu Ezaki, Tatsuhiko Kodama, Kristina Schoonjans, Antonio C Bianco, and Johan Auwerx. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation.. In Nature, volume 439, number 7075, pages 484-9, 2006. 28. Angelina Rodriguez, Angeles Durán, Mohammed Selloum, Marie-France Champy, Francisco J Diez-Guerra, Juana María Flores, Manuel Serrano, Johan Auwerx, María T Diaz-Meco, and Jorge Moscat. Mature-onset obesity and insulin resistance in mice deficient in the signaling adapter p62.. In Cell metabolism, volume 3, number 3, pages 211-22, 2006. 29. Jean-Francois Louet, Agnès Coste, Larbi Amazit, Mounia Tannour-Louet, Ray-Chang Wu, Sophia Y Tsai, Ming-Jer Tsai, Johan Auwerx, and Bert W O'Malley. Oncogenic steroid receptor coactivator-3 is a key regulator of the white adipogenic program.. In Proceedings of the National Academy of Sciences of the United States of America, volume 103, number 47, pages 17868-73, 2006. 30. Marie Lagouge, Carmen Argmann, Zachary Gerhart-Hines, Hamid Meziane, Carles Lerin, Frederic Daussin, Nadia Messadeq, Jill Milne, Philip Lambert, Peter Elliott, Bernard Geny, Markku Laakso, Pere Puigserver, and Johan Auwerx. Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha.. In Cell, volume 127, number 6, pages 1109-22, 2006. 31. David H Volle, Rajesha Duggavathi, Benjamin C Magnier, Sander M Houten, Carolyn L Cummins, Jean-Marc A Lobaccaro, Guido Verhoeven, Kristina Schoonjans, and Johan Auwerx. The small heterodimer partner is a gonadal gatekeeper of sexual maturation in male mice.. In Genes & development, volume 21, number 3, pages 303-15, 2007. 32. Nassim Dali-Youcef, Chikage Mataki, Agnès Coste, Nadia Messaddeq, Sylvain Giroud, Stéphane Blanc, Christian Koehl, Marie-France Champy, Pierre Chambon, Lluis Fajas, Daniel Metzger, Kristina Schoonjans, and Johan Auwerx. Adipose tissue-specific inactivation of the retinoblastoma protein protects against diabesity because of increased energy expenditure.. In Proceedings of the National Academy of Sciences of the United States of America, volume 104, number 25, pages 10703-8, 2007. 33. Agnes Coste, Laurent Dubuquoy, Romain Barnouin, Jean-Sebastien Annicotte, Benjamin Magnier, Mario Notti, Nadia Corazza, Maria Cristina Antal, Daniel Metzger, Pierre Desreumaux, Thomas Brunner, Johan Auwerx, and Kristina Schoonjans. LRH-1-mediated glucocorticoid synthesis in enterocytes protects against inflammatory bowel disease.. In Proceedings of the National Academy of Sciences of the United States of America, volume 104, number 32, pages 13098-103, 2007. 34. Roberto Pellicciari, Hiroyuki Sato, Antimo Gioiello, Gabriele Costantino, Antonio Macchiarulo, Bahman M Sadeghpour, Gianluca Giorgi, Kristina Schoonjans, and Johan Auwerx. Nongenomic actions of bile acids. Synthesis and preliminary characterization of 23- and 6,23-alkyl-substituted bile acid derivatives as selective modulators for the G-protein coupled receptor TGR5.. In Journal of medicinal chemistry, volume 50, number 18, pages 4265-8, 2007. 35. Chikage Mataki, Benjamin C Magnier, Sander M Houten, Jean-Sébastien Annicotte, Carmen Argmann, Charles Thomas, Henk Overmars, Wim Kulik, Daniel Metzger, Johan Auwerx, and Kristina Schoonjans. Compromised intestinal lipid absorption in mice with a liver-specific deficiency of liver receptor homolog 1.. In Molecular and cellular biology, volume 27, number 23, pages 8330-9, 2007. 36. Françoise Gofflot, Nathalie Chartoire, Laurent Vasseur, Sami Heikkinen, Doulaye Dembele, Julie Le Merrer, and Johan Auwerx. Systematic gene expression mapping clusters nuclear receptors according to their function in the brain.. In Cell, volume 131, number 2, pages 405-18, 2007. 37. Hiroyuki Sato, Antonio Macchiarulo, Charles Thomas, Antimo Gioiello, Mizuho Une, Alan F Hofmann, Régis Saladin, Kristina Schoonjans, Roberto Pellicciari, and Johan Auwerx. Novel potent and selective bile acid derivatives as TGR5 agonists: biological screening, structure-activity relationships, and molecular modeling studies.. In Journal of medicinal chemistry, volume 51, number 6, pages 1831-41, 2008. 38. Rajesha Duggavathi, David H Volle, Chikage Mataki, Maria C Antal, Nadia Messaddeq, Johan Auwerx, Bruce D Murphy, and Kristina Schoonjans. Liver receptor homolog 1 is essential for ovulation.. In Genes & development, volume 22, number 14, pages 1871-6, 2008. 39. Agnès Coste, Jean-Francois Louet, Marie Lagouge, Carles Lerin, Maria Cristina Antal, Hamid Meziane, Kristina Schoonjans, Pere Puigserver, Bert W O'Malley, and Johan Auwerx. The genetic ablation of SRC-3 protects against obesity and improves insulin sensitivity by reducing the acetylation of PGC-1{alpha}.. In Proceedings of the National Academy of Sciences of the United States of America, volume 105, number 44, pages 17187-92, 2008. 40. Jérôme N Feige, Marie Lagouge, Carles Canto, Axelle Strehle, Sander M Houten, Jill C Milne, Philip D Lambert, Chikage Mataki, Peter J Elliott, and Johan Auwerx. Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation.. In Cell metabolism, volume 8, number 5, pages 347-58, 2008. 41. Sami Heikkinen, Carmen Argmann, Jérôme N Feige, Hana Koutnikova, Marie-France Champy, Nassim Dali-Youcef, Eric E Schadt, Markku Laakso, and Johan Auwerx. The Pro12Ala PPARgamma2 variant determines metabolism at the gene-environment interface.. In Cell metabolism, volume 9, number 1, pages 88-98, 2009. 42. Carles Cantó, Zachary Gerhart-Hines, Jerome N Feige, Marie Lagouge, Lilia Noriega, Jill C Milne, Peter J Elliott, Pere Puigserver, and Johan Auwerx. AMPK regulates energy expenditure by modulating NAD(+) metabolism and SIRT1 activity.. In Nature, volume 458, number 7241, pages 1056-1060, 2009. 43. Hana Koutnikova, Markku Laakso, Lu Lu, Roy Combe, Jussi Paananen, Teemu Kuulasmaa, Johanna Kuusisto, Hans-Ulrich Häring, Torben Hansen, Oluf Pedersen, Ulf Smith, Markolf Hanefeld, Robert W Williams, and Johan Auwerx. Identification of the UBP1 locus as a critical blood pressure determinant using a combination of mouse and human genetics. In PLoS Genetics, volume 5, number 8, page e1000591, 2009. CVName: Johan (first), Henri (middle) AUWERX Office Address: Ecole Polytechnique Fédérale de Lausanne 1015 Lausanne, Switzerland Place of birth: Diepenbeek, Belgium Education: 1967-1975 College (Summa cum laude) St-Jozefscollege, Hasselt, Belgium 1975-1978 Bachelor Medical Sciences (Magna cum laude) Katholieke Universiteit Leuven, Belgium 1978-1982 Medical Doctor (M.D.; Summa cum laude) Katholieke Universiteit Leuven, Belgium 1986-1990 Doctor of Philosophy (Ph.D.) Katholieke Universiteit Leuven, Belgium Dissertation: Regulation of genes involved in lipid metabolism in the macrophage Post-doctoral training: 1986 Research Fellow Molecular Endocrinology Katholieke Universiteit Leuven, Belgium 1986-1989 Research Fellow Molecular Endocrinology University of Washington, Seattle, WA 1989 EMBO Fellow Molecular Biology Laboratoire de Génétique Moléculaire des Eucaryotes, Strasbourg, France Licensure and Certification: 1982 License as Medical Doctor, Belgium 1982 ECFMG (Educational Commission for Foreign Medical Graduates) certificate on basis of the VISA qualifying examination (certificate # 352-705-8) 1987 License as Specialist in Internal Medicine, Belgium 1991 License as Medical Doctor, France Academic Appointments: 1988-1991 Research Associate NFWO, Katholieke Universiteit Leuven, Belgium 1991-1999 Research Director (~ Full Professor) CNRS, Institut Pasteur de Lille, France 1999-2003 Research Director (~ Full Professor) CNRS, Institut de Génétique et Biologie Moléculaire et Cellulaire, Illkirch, France 2003-2008 Professor of Medicine Université Louis Pasteur, Strasbourg, France 2007- Visiting Professor Harvard Medical School, Boston, MA 2008- Full Professor Ecole Polytechnique Fédérale Lausanne, Switzerland Hospital or Affiliated Institution Appointments: 1982-1985 Resident in Medicine University Hospital Gasthuisberg, Leuven, Belgium 1985-1986 Fellow in Endocrinology & Metabolism University Hospital Gasthuisberg, Leuven, Belgium 1986-1988 Fellow in Endocrinology & Metabolism University of Washinghton, Seattle, USA 1988-1991 Consultant Endocrinology & Metab. University Hospital Gasthuisberg, Leuven, Belgium Awards and Honors: 1985 Horlait-Dapsens prize for medical research; Belgium 1986 NATO travel grant; NATO countries Fellowship Belgian American Educational Foundation; USA/Belgium Fullbright award; USA Travel award Belgian National Foundation for Research; Belgium 1987 J.Fogarty international research fellowship (NIH); USA 1989 F. De Waele prize for cancer research; Belgium Morgagni Young Investigator Award on Metabolism; Italy Boehringer-Mannheim prize for Atherosclerosis; Belgium 1992 Belgian Endocrine Society Award; Belgium 1993 Prix Danone "Santé et Nutrition"; France 1998 Prix de la Fondation pour la Recherche Médicale; France Minkowski Prize, European Association for the Study of Diabetes; Europe (Euro). Spa Prize for Nutrition; Belgium 2001 6th Dalan Boyd Pritchett Lecture, University of Pennsylvania, PA 2003 EMBO member. 2004 Morgagni Gold Medal for Metabolism: Italy 2005 Prix Jean Valade de la Fondation de France 2006 Josiah Brown Lecture Award, UCLA, CA |
