MCB
Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Luo, J.
Right arrow Articles by Giguère, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Luo, J.
Right arrow Articles by Giguère, V.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, November 2003, p. 7947-7956, Vol. 23, No. 22
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.22.7947-7956.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Reduced Fat Mass in Mice Lacking Orphan Nuclear Receptor Estrogen-Related Receptor {alpha}

Jiangming Luo,1 Robert Sladek,1 Julie Carrier,1 Jo-Ann Bader,1 Denis Richard,2 and Vincent Giguère1*

Molecular Oncology Group, Department of Medicine, McGill University Health Centre, Montréal, Québec, Canada H3A 1A1,1 Département d'Anatomie et Physiologie, Faculté de Médecine, Université Laval, Québec, Canada G1K 7P42

Received 31 March 2003/ Returned for modification 9 May 2003/ Accepted 30 July 2003

The estrogen-related receptor {alpha} (ERR{alpha}) is an orphan member of the superfamily of nuclear hormone receptors expressed in tissues that preferentially metabolize fatty acids. Despite the molecular characterization of ERR{alpha} and identification of target genes, determination of its physiological function has been hampered by the lack of a natural ligand. To further understand the in vivo function of ERR{alpha}, we generated and analyzed Estrra-null (ERR{alpha}-/-) mutant mice. Here we show that ERR{alpha}-/- mice are viable, fertile and display no gross anatomical alterations, with the exception of reduced body weight and peripheral fat deposits. No significant changes in food consumption and energy expenditure or serum biochemistry parameters were observed in the mutant animals. However, the mutant animals are resistant to a high-fat diet-induced obesity. Importantly, DNA microarray analysis of gene expression in adipose tissue demonstrates altered regulation of several enzymes involved in lipid, eicosanoid, and steroid synthesis, suggesting that the loss of ERR{alpha} might interfere with other nuclear receptor signaling pathways. In addition, the microarray study shows alteration in the expression of genes regulating adipogenesis as well as energy metabolism. In agreement with these findings, metabolic studies showed reduced lipogenesis in adipose tissues. This study suggests that ERR{alpha} functions as a metabolic regulator and that the ERR{alpha}-/- mice provide a novel model for the investigation of metabolic regulation by nuclear receptors.

* Corresponding author. Mailing address: Molecular Oncology Group, McGill University Health Centre, 687 Pine Ave. West, Montréal, Québec, Canada H3A 1A1. Phone: (514) 843-1406. Fax: (514) 843-1478. E-mail: vincent.giguere{at}mcgill.ca.

Molecular and Cellular Biology, November 2003, p. 7947-7956, Vol. 23, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.22.7947-7956.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:



Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
J. Bacteriol. J. Virol. Eukaryot. Cell
Microbiol. Mol. Biol. Rev. Clin. Vaccine Immunol. All ASM Journals

Copyright © 2003 by the American Society for Microbiology. All rights reserved.