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Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor α.
Open accessAbstract
The estrogen-related receptor alpha (ERRalpha) is an orphan member of the superfamily of nuclear hormone receptors expressed in tissues that preferentially metabolize fatty acids. Despite the molecular characterization of ERRalpha 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 ERRalpha, we generated and analyzed Estrra-null (ERRalpha-/-) mutant mice. Here we show that ERRalpha-/- 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 ERRalpha 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 ERRalpha functions as a metabolic regulator and that the ERRalpha-/- mice provide a novel model for the investigation of metabolic regulation by nuclear receptors.
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“Interestingly, ERR␣-null mice have reduced body weight and are normoglycemic, in parallel with up-regulation of medium-chain acyl-CoA dehydrogenase and reduced lipogenesis, both of which may contribute to resistance to diet-induced obesity (277).”
From The role of mitochondria in the pathogenesis of type 2 diabetes (2010) · cites this paper as [277]
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Metadata
- Authors
- Luo, J., Sladek, R., Carrier, J., Bader, J.-A., Richard, D., & Giguère, V.
- Affiliations
- McGill University Health Centre (CA)
- Université Laval (CA)
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2003-11-01
- Volume
- 23
- Issue
- 22
- Pages
- 7947-7956
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC262360
- OpenAlex
- W2172200901
- Cited by
- 370
- References
- 75
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 10 · 2023: 11 · 2022: 14 · 2021: 16 · 2020: 12 · 2019: 12 · 2018: 14 · 2017: 14 · 2016: 12 · 2015: 17 · 2014: 13 · 2013: 22 · 2012: 18
- FWCI
- 6.56
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Health Research
- Canadian Institutes of Health Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- estrogen-related receptor alpha, fat mass, high-fat diet-induced obesity, adipose tissue gene expression, lipogenesis, adipogenesis, energy metabolism, nuclear receptors, eicosanoid biosynthesis, steroid synthesis, metabolic regulation
- MeSH terms
- ERRalpha Estrogen-Related Receptor, Adipose Tissue, Animals, Body Weight, Dietary Fats, Energy Metabolism, Female, Lipids, Male, Mice, Inbred C57BL, Obesity, Organ Size, Phenotype, Receptors, Estrogen, Signal Transduction, Receptors, Cytoplasmic and Nuclear, Mice, Knockout, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice
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