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MicroRNAs in Diabetes

English title MicroRNAs in Diabetes
Applicant Stoffel Markus
Number 137145
Funding scheme ProDoc
Research institution Molekulare Gesundheitswissenschaften Departement Biologie ETH Zürich
Institution of higher education ETH Zurich - ETHZ
Main discipline Endocrinology
Start/End 01.01.2012 - 31.12.2014
Approved amount 226'482.00
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All Disciplines (2)

Discipline
Endocrinology
Molecular Biology

Keywords (3)

microRNA; brown adipocyte tissue; metabolism

Lay Summary (English)

Lead
Lay summary

The epidemic rise of obesity and diabetes mellitus imposes increasing economic and public health burdens. The discovery of microRNAs (miRs) as a novel class of non- coding RNAs about 10 years ago has added new layers to our understanding of gene regulation, how metabolism is regulated and offers new therapeutic strategies to combat metabolic diseases such as diabetes. MicroRNAs control gene expression at the posttranscriptional level and have been demonstrated to regulate major metabolic pathways such as insulin secretion and cholesterol synthesis. Recent preliminary data from our laboratory indicates that microRNAs could have further unexpected roles for energy homeostasis in brown adipocytes. Brown adipose tissue (BAT) is a mitochondria-rich tissue with important roles in lipid catabolism and thermogenesis. The primary function of brown fat is to generate body heat in non- shivering animals that is produced by alternative route for protons that uncouples oxidative phosphorylation and instead release the energy in the proton motif force as heat. How this regulation of the participating metabolic networks is regulated at the molecular level, however, is incompletely understood. Recently, we showed that the expression of a discrete set of microRNAs formerly thought to be muscle-specific, namely miR-1, miR-133, miR-208 and miR-206, in BAT. Furthermore, we demonstrated that the expression levels of these microRNAs in BAT is cold-responsive. We will combine loss-of function and gain-of function approaches in BAT to investigate the role of miR-1, miR-133 and miR-206 for the expression of uncoupling proteins and mitochondrial function in brown adipocytes. Mouse models and adenoviral constructs we be generated to study the physiological role of myomirs in BAT and to identify using unbiased experimental approaches conserved microRNA target genes. We anticipate that the discovery of microRNAs that are specific for BAT and muscle will reveal novel mechanisms that control energy expenditure and might lead to therapeutic strategies to protect against obesity and diabetes.


Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
The microRNA-200 family regulates pancreatic beta cell survival in type 2 diabetes
Belgardt et al (2015), The microRNA-200 family regulates pancreatic beta cell survival in type 2 diabetes, in Nature Medicine, 21(6), 619-627.
MyomiR-133 regulates brown fat differentiation through Prdm16
Trajkovski Mirko et al. (2012), MyomiR-133 regulates brown fat differentiation through Prdm16, in Nature Cell Biology, 14(12), 1330-1336.

Collaboration

Group / person Country
Types of collaboration
Research groups Krek, Moch, Peter and Frew from ETH Zurich and University Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
Research groups Werner, Kopf and Rogler at ETH Zurich and University Zurich Switzerland (Europe)
- in-depth/constructive exchanges on approaches, methods or results
- Research Infrastructure
- Exchange of personnel

Scientific events

Active participation

Title Type of contribution Title of article or contribution Date Place Persons involved
EMBO|EMBL Symposium “Translating Diabetes” Talk given at a conference Regulation of miRNA in metabolism 30.04.2014 European Molecular Biology Laboratory, Heidelberg, Germany, Germany Balaghy Mobin Mehrpouya; Stoffel Markus;
Keystone Symposium "RNA Silencing" Talk given at a conference miRNA function in metabolism 03.02.2014 Seattle, WA, United States of America Stoffel Markus;
International Diabetes Federation, World Diabetes Congress 2013 Talk given at a conference MicroRNAs and insulin resistance 04.12.2013 Melbourne, Australia Stoffel Markus;
Sanford Burnham Medical Institute Individual talk Role of microRNAs in Metabolism 14.11.2013 Orlando, United States of America Stoffel Markus;
Cold Spring Harbor Meeting Metabolic Signaling and Disease: From Cell to Organism Talk given at a conference MicroRNAs regulating metabolism 17.08.2013 Cold Spring Harbor , United States of America Stoffel Markus;
Keystone Symposium New Insights into Mechanism of Disease and its Treatment Talk given at a conference MicroRNAs in pancreatic beta cell function 28.01.2013 Keystone, CO, United States of America Stoffel Markus;


Self-organised

Title Date Place

Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Ein Molekül gegen Übergewicht Freiburger Nachrichten International 2012
Media relations: print media, online media http://de.500healthy.com/page/they-discover-a-method-to-facilitate-fat-burning.html German-speaking Switzerland 2012
Media relations: print media, online media Molekül zwingt Sie, Gewicht zu verlieren Medifact German-speaking Switzerland Western Switzerland International 2012
Media relations: print media, online media Züricher Forscher findet Fettabbau Molekül Tagesanzeiger_Zurich Western Switzerland German-speaking Switzerland 2012

Awards

Title Year
G.B. Morgagni Prize (Gold Medal) 2012

Patents

Title Date Number Inventor Owner
Targeting MicroRNAs for metabolic disorders 18.07.2014 9243249

Abstract

The epidemic rise of obesity and diabetes mellitus imposes increasing economic and public health burdens. The discovery of microRNAs (miRs) as a novel class of non-coding RNAs about 10 years ago has added new layers to our understanding of how metabolism is regulated and offers new therapeutic strategies. MicroRNAs control gene expression at the posttranscriptional level and have been demonstrated to regulate major metabolic pathways such as insulin secretion and cholesterol synthesis. Recent evidence indicates that microRNAs could have further unexpected roles for energy homeostasis. Brown adipose tissue (BAT) and skeletal muscle are both mitochondria-rich tissues with important roles in lipid catabolism. The response of BAT and skeletal muscle to environmental stimuli is often synergistic. How this coordination is regulated at the molecular level, however, is incompletely understood. Recently, the expression of a discrete set of microRNAs formerly thought to be muscle-specific, miR-1, miR-133 and miR-206, has also been detected in BAT and we can now show that the expression levels of these microRNAs in BAT is cold-responsive. These findings indicate that the function of BAT and muscle could be coordinated by a common set of microRNAs. We will start a collaborative effort and join our expertise in adipocytes (Stoffel group) and muscle cells (Krützfeldt group) to study the function of this unique set of microRNAs that are specific to BAT and skeletal muscle. We will combine loss-of function and gain-of function approaches in BAT as well as primary muscle cells to investigate the role of miR-1, miR-133 and miR-206 for the expression of uncoupling proteins and mitochondrial function in these cell types. We will share mouse models and adenoviral constructs and we anticipate that the parallel investigation of BAT and skeletal muscle will greatly facilitate the identification of conserved microRNA target genes. The discovery of microRNAs that are specific for BAT and muscle could reveal novel mechanisms that control energy expenditure and might lead to therapeutic strategies to protect against obesity.
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