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Genètica i Biologia Molecular de Proteïnes Mitocondrials i patologies associades
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Departament de Bioquímica i Biologia Molecular
Facultat de Biologia (UB)
Avda. Diagonal, 645
Edifici nou Pl. -1
08028 Barcelona
Tel 93-4021523 / 606148772
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LAST PAPER

Peroxisome Proliferator-activated Receptor-γ Coactivator-1α Controls Transcription of the Sirt3 Gene, an Essential Component of the Thermogenic Brown Adipocyte Phenotype

Albert Giralt, Elayne Hondares, Josep A. Villena, Francesc Ribas, Julieta Díaz-Delfín, Marta Giralt, Roser Iglesias and Francesc Villarroya

From the Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, and CIBER Fisiopatologia de la Obesidad y Nutrición, and the Institut de Recerca Vall d'Hebron.

J Biol Chem. 2011 May 13;286(19):16958-66. Epub 2011 Mar 27.

Abstract
Sirt3 (silent mating type information regulation 2, homolog 3), a member of the sirtuin family of protein deacetylases with multiple actions on metabolism and gene expression is expressed in association with brown adipocyte differentiation. Using Sirt3-null brown adipocytes, we determined that Sirt3 is required for an appropriate responsiveness of cells to noradrenergic, cAMP-mediated activation of the expression of brown adipose tissue thermogenic genes. The transcriptional coactivator Pgc-1α (peroxisome proliferator-activated receptor-γ coactivator-1α) induced Sirt3 gene expression in white adipocytes and embryonic fibroblasts as part of its overall induction of a brown adipose tissue-specific pattern of gene expression. In cells lacking Sirt3, Pgc-1α failed to fully induce the expression of brown fat-specific thermogenic genes. Pgc-1α activates Sirt3 gene transcription through coactivation of the orphan nuclear receptor Err (estrogen-related receptor)-α, which bound the proximal Sirt3 gene promoter region. Errα knockdown assays indicated that Errα is required for full induction of Sirt3 gene expression in response to Pgc-1α. The present results indicate that Pgc-1α controls Sirt3 gene expression and this action is an essential component of the overall mechanisms by which Pgc-1α induces the full acquisition of a brown adipocyte differentiated phenotype.

 
 
LABORATORY OF RESEARCH IN GENETICS AND MOLECULAR BIOLOGY OF MITOCHONDRIAL PROTEINS AND ASSOCIATED DISEASES

Department of Biochemistry and Molecular Biology
Faculty of Biology
University of Barcelona
 

Our laboratory is specialized in the study of the molecular and cell biology of the control of mitochondrial energy metabolism and associated diseases.

We study the molecular mechanisms of transcriptional control of the differentiation of specialized cell types with key roles in energy homeostasis (adipocytes, muscle cells,...) as well as how metabolic and endocrine functions are regulated in cells and tissues. For this purpose, we use experimental models at a sub-cellular (mitochondria), cellular (cell culture) and animal (gene-modified rodent models) levels of analysis. This is complemented by studying directly samples from patients with metabolic diseases (obesity, lipodystrophy, diabetes,...).

Our aim is to identify the main molecular actors that control energy metabolism in health and disease, and by this means to establish foreseeable prevention and treatment strategies to ameliorate complex metabolic diseases.


NEWS
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"A report and interview with Francesc Villarroya in the Newsletter of CIBERobn"
 
A report in the newspaper "El País" summarizes the current advancements in brown adipose tissue research in relation to obesity and quote the opinions of F Villarroya among other experts.
 


Our research group is contributing to scientific spreading: “Brown fat and Obesity” in the April issue of “Investigación y Ciencia”, the Spanish version of Scientific American.
  In the section “`Panorama”, Francesc Villarroya, Roser Iglesias and Marta Giralt summarize the recent evidence of the importance of brown fat in adult humans and its role in energy expenditure and the control of obesity.

 

Full Article

 
A novel contribution of our research team on the role of brown adipose tissue in FGF21 biology, published in Journal of Biological Chemistry
 

We report that brown adipose tissue is not only a target but also a source of the hormonal factor FGF21 after activation of thermogenesis. This discovery may be the tip of the iceberg of the recognition of a novel endocrine role of brown fat as source of regulatory molecules with impact in overall metabolism.

The paper is already available on-line at http://www.ncbi.nlm.nih.gov/pubmed/21317437

The Figure at the end of the study summarizes the major findings.
The December 2010 issue of the journal Current Pharmaceutical Design, with the title "Targets of Metabolic Toxicity of HIV Antiretroviral Drugs: The Multiple Roads to Lipodystrophy and Metabolic Syndrome", has been edited by our research team in collaboration with P. Domingo.
 

The December issue of Current Pharmaceutical Design has been devoted to "Targets of Metabolic Toxicity of HIV Antiretroviral Drugs: The Multiple Roads to Lipodystrophy and Metabolic Syndrome".  Francesc Villarroya, in collaboration with Pere Domingo, acted as executive guest editor of this issue. The issue includes several review articles on the distinct aspects of the ethiopathogenesis of lipodystrophy syndrome and the metabolic alterations appearing in HIV-1-infected patients under antiretroviral treatment. Adipose cell alterations, inflammation, lipotoxicity and pharmacogenomics of the syndrome are among the subjects covered. The most recognized international experts in the field have participated in the issue. The cover of the journal depicts the lipotoxic events associated with these metabolic alterations in HIV-1 patients.

The XI International Congress on Obesity rewards a research work of our team
 

The XI International Congress on Obesity, held in Stockholm, has distinguished the communication “ FGF21, a novel actor in the control of brown adipose tissue activation Thermogenics” presented by our team as one of the top five communications.

This communication was selected among 1,250 worldwide research projects. Specifically, it has been considered the best communication in the field of Experimental Medicine and Physiology (one of the five areas of research in the Congress).

An article on the discovery of a new pathway of thermogenesis hormonal control, carried out by our research team,  on “Cell Metabolism” cover.
 

The publication, edited on “ Cell Metabolism” March issue, identifies the hormonal  factor FGF21 as a new activator of brown adipose tissue and its metabolic consumption activity. FGF21 is produced by the liver that releases it into the circulation in response to the stimulation of fatty acids. The study, based on the use of neonatal mice as an experimental model which are exposed to milk fat for the first time in their development, identifies a new pathway of controlling the energy expenditure with potential therapeutic application in obesity and type II diabetes.
 
 
   
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