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MicroRNAs role in brown and white adipose tissue differentiation and function

English title MicroRNAs role in brown and white adipose tissue differentiation and function
Applicant Trajkovski Mirko
Number 144886
Funding scheme SNSF Professorships
Research institution Département de physiologie cellulaire et métabolisme Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Physiology : other topics
Start/End 01.08.2013 - 31.07.2017
Approved amount 1'598'454.00
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All Disciplines (7)

Discipline
Physiology : other topics
Metabolic Disorders
Nutritional Research, Vitaminology
Genetics
Cellular Biology, Cytology
Pathophysiology
Endocrinology

Keywords (8)

Physiology; Diabetes; Metabolism; Systems biology; Preadipocytes; Obesity; MicroRNAs; Brown and white adipose tissue

Lay Summary (French)

Lead
Une augmentation de l’apport calorique et/ou une diminution de la dissipation d’énergie entraîne le développement d’un syndrome d’obésité.
Lay summary

Les Mammifères ont deux types de tissu adipeux dont les fonctions sont différentes. Le tissu adipeux blanc est un régulateur important de la balance énergétique, servant à stocker l’excès d’énergie sous forme de lipides. Un tel excès d’énergie entraîne divers dysfonctionnements métaboliques pouvant mener au diabète, à la dyslipidémie (altération du métabolisme des lipides), à l’athérosclérose et à d’autres pathologies. La fonction principale du tissu adipeux brun est de consommer les lipides pour produire de la chaleur, fonction qui est induite par la consommation d’un repas ou l’exposition au froid. Une augmentation de la quantité de tissu adipeux brun provoque une élévation de la dépense énergétique et une diminution du poids corporel, améliorant l’état de santé des patients ou des modèles animaux atteints d’obésité sans affecter la fonction d’autres tissus. Dans l’ensemble, ces observations soulignent l’intérêt thérapeutique que peut avoir la modulation des réserves adipeuses.

Le projet proposé vise à identifier de petites molécules d’ARN, appelées microARN, ainsi que d’autres facteurs qui contrôlent la différenciation ou la fonction des tissus adipeux blanc ou brun. Nous déterminerons l’origine des adipocytes bruns et établirons leur importance, en utilisant à la fois des cellules et des modèles murins. Ceci permettra de développer de nouvelles stratégies visant à induire l’activité du tissu adipeux brun et à augmenter sa quantité par le biais d’approches génétiques et pharmacologiques. Nous mettrons également au point des techniques permettant de cibler et de moduler les microARN du tissu adipeux brun de façon spécifique, ce qui permettra non seulement d’investiguer la fonction de ces molécules dans ce tissu mais aussi de développer de nouvelles stratégies pour traiter les dyslipidémies, le diabète et l’obésité.

 

Direct link to Lay Summary Last update: 15.11.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1
Rathjen Thomas, Yan Xin, Kononenko Natalia L, Ku Min-Chi, Song Kun, Ferrarese Leiron, Tarallo Valentina, Puchkov Dmytro, Kochlamazashvili Gaga, Brachs Sebastian, Varela Luis, Szigeti-Buck Klara, Yi Chun-Xia, Schriever Sonja C, Tattikota Sudhir Gopal, Carlo Anne Sophie, Moroni Mirko, Siemens Jan, Heuser Arnd, van der Weyden Louise, Birkenfeld Andreas L, Niendorf Thoralf, Poulet James F A, Horvath Tamas L, et al. (2017), Regulation of body weight and energy homeostasis by neuronal cell adhesion molecule 1, in Nature Neuroscience, -.
Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling
Fabbiano S, Suárez-Zamorano N, Rigo D, Veyrat-Durebex C, Stevanovic Dokic A, Colin DJ, Trajkovski M (2016), Caloric Restriction Leads to Browning of White Adipose Tissue through Type 2 Immune Signaling, in Cell Metabolism, 534(7606), 185-187.
Physiology: Microbial signals to the brain control weight
Trajkovski Mirko, Wollheim Claes B. (2016), Physiology: Microbial signals to the brain control weight, in Nature, 534(7606), 185-187.
Physiology: Microbial signals to the brain control weight.
Trajkovski M Wollheim CB. (2016), Physiology: Microbial signals to the brain control weight., in Nature, 534(7606), 185-187.
Gut Microbiota Orchestrates Energy Homeostasis during Cold
Chevalier Claire, Stojanović Ozren, Colin Didier J., Suarez-Zamorano Nicolas, Tarallo Valentina, Veyrat-Durebex Christelle, Rigo Dorothée, Fabbiano Salvatore, Stevanović Ana, Hagemann Stefanie, Montet Xavier, Seimbille Yann, Zamboni Nicola, Hapfelmeier Siegfried, Trajkovski Mirko (2015), Gut Microbiota Orchestrates Energy Homeostasis during Cold, in Cell, 163(6), 1360-1374.
Microbiota depletion promotes browning of white adipose tissue and reduces obesity
Suárez-Zamorano Nicolas, Fabbiano Salvatore, Chevalier Claire, Stojanović Ozren, Colin Didier J, Stevanović Ana, Veyrat-Durebex Christelle, Tarallo Valentina, Rigo Dorothée, Germain Stéphane, Ilievska Miroslava, Montet Xavier, Seimbille Yann, Hapfelmeier Siegfried, Trajkovski Mirko (2015), Microbiota depletion promotes browning of white adipose tissue and reduces obesity, in Nature Medicine, 21(12), 1497-1501.
Gut Microbiota Orchestrates Energy Homeostasis during Cold.
Chevalier Claire Stojanović Ozren ... Trajkovski Mirko (2015), Gut Microbiota Orchestrates Energy Homeostasis during Cold., in Cell, 163((6)), 1360-1374.
MicroRNAs Are Required for the Feature Maintenance and Differentiation of Brown Adipocytes
Kim H.-J., Cho H., Alexander R., Patterson H. C., Gu M., Lo K. A., Xu D., Goh V. J., Nguyen L. N., Chai X., Huang C. X., Kovalik J.-P., Ghosh S., Trajkovski M., Silver D. L., Lodish H., Sun L. (2014), MicroRNAs Are Required for the Feature Maintenance and Differentiation of Brown Adipocytes, in Diabetes, 63(12), 4045-4056.
MicroRNAs are required for the feature maintenance and differentiation of brown adipocytes.
Kim HJ Cho H Alexander R Patterson HC Gu M Lo KA Xu D Goh VJ Nguyen LN Chai X Huang CX Ko (2014), MicroRNAs are required for the feature maintenance and differentiation of brown adipocytes., in Diabetes, 63(12), 4045-4056.
MiR-27 orchestrates the transcriptional regulation of brown adipogenesis
Sun Lei, Trajkovski Mirko (2014), MiR-27 orchestrates the transcriptional regulation of brown adipogenesis, in Metabolism, 63(2), 272-282.
MicroRNA networks regulate development of brown adipocytes
Trajkovski Mirko, Lodish Harvey (2013), MicroRNA networks regulate development of brown adipocytes, in Trends Endocrinol Metab, 24(9), 442-450.

Collaboration

Group / person Country
Types of collaboration
Duke University Singapore Singapore (Asia)
- in-depth/constructive exchanges on approaches, methods or results
- Publication
- Research Infrastructure
University of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
University of Geneva Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Exchange of personnel
Max Delbrück Center for Molecular Medicine Germany (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
University of Bern Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
IHMC Congress Talk given at a conference Gut microbiota and energy homeostasis 09.11.2016 Houston, United States of America Trajkovski Mirko;
Frontier in Immunometabolism Talk given at a conference Energy homeostasis in health and metabolic disease 19.04.2016 Hong Kong, Hongkong Trajkovski Mirko;
UNIL Seminar (Génopode- Sorge - Auditorium B) Individual talk Bugs, drugs and miRNAs: energy balance from fat and gut 27.04.2015 Lausanne, Switzerland Trajkovski Mirko;
Frontiers in Obesity Research Individual talk Role of miRNAs in brown and white adipose tissue differentiation and function 10.11.2014 Santiago de Compostela, Spain Trajkovski Mirko;
22ème réunion des Groupes de recherche en Endocrinologie et Diabétologie de la région Rhône-Alpes (G2L2) Talk given at a conference MicroRNA networks regulate development of brown adipocytes 23.05.2014 Grenoble, France Trajkovski Mirko;


Self-organised

Title Date Place
Keystone symposia 01.03.2015 Keystone, Colorado, United States of America
American Diabetes Association - 74th Scientific Sessions (2014) 12.06.2014 San Francisco, United States of America
10th Annual Meeting of the Swiss Stem Cells Network (Involved as a poster reviewer) 04.06.2014 Geneva, Switzerland

Communication with the public

Communication Title Media Place Year
Media relations: radio, television Cold exposure and brown fat RTS Western Switzerland 2015
Media relations: print media, online media Cold-weather friends The Economist International 2015
Media relations: print media, online media How Bacteria and Brown Fat Can Spur Weight Loss Time International 2015
Media relations: radio, television Le froid et une bactérie intestinale particulière pourraient influencer notre poids RTS Western Switzerland 2015
Media relations: print media, online media raté flore intestinale peut déclencher l'obésité Tribune de Geneve Western Switzerland 2015
Media relations: print media, online media Scientists discover link between temperature and fat loss The Independent International 2015

Awards

Title Year
Prix Alex F Müller de physiopathologie given to our work: Gut Microbiota Orchestrates Energy Homeostasis during Cold. Cell. 2015 Dec 3;163(6):1360-74. 2016

Associated projects

Number Title Start Funding scheme
172906 Metabolic homeostasis through physiological stimulation of beige fat development 01.08.2017 SNSF Professorships

Abstract

Mammals have two types of fat: brown and white, with opposing functions. The white adipose tissue (WAT) is an important regulator of the whole body homeostasis that also serves to store energy in form of triglycerides (TGs). The main function of the brown adipose tissue (BAT) is to catabolize lipids in order to produce heat, a function that can be induced by cold exposure or diet. Disruption of the normal differentiation or development of the WAT causes ectopic lipid storage and severe pathology in both humans and experimental animals. Increased BAT development leads to increased energy expenditure without causing dysfunction in other tissues, and is associated with a lean and healthy phenotype, outlining the manipulation of the fat stores as an obvious therapeutic objective. With the proposed research we will identify miRNAs and other factors that regulate BAT and WAT differentiation and function. Using in vitro and in vivo systems, cohorts of human patients, as well as linage tracing studies we will also determine the origin of the brown fat cells within the subcutaneous fat, establish their importance in the regulation of metabolism in vivo, and develop novel strategies to induce the brown fat differentiation and function. By discovering ways to exclusively deliver and silence miRNAs in fat/brown fat will allow us not only to investigate the miRNAs function specifically in the brown fat, but also to develop new strategies for treatment of dyslipedaemia, diabetes and obesity.
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