Cited by 373Peroxisome Proliferator-Activated ReceptorsAdipose Tissue and MetabolismEstrogen and related hormone effects

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Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor α.

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Luo, Jiangming, Sladek, Robert, Carrier, Julie, Bader, Jo-Ann, Richard, Denis, Giguère, Vincent·2003·Molecular and Cellular Biology

DOI 10.1128/mcb.23.22.7947-7956.2003PMC PMC262360

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Abstract

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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Authors: Luo, J., Sladek, R., Carrier, J., Bader, J.-A., Richard, D., & Giguère, V.
Affiliations: McGill University Health Centre (CA)
Université Laval (CA)
ORCID: Sladek, Robert
Richard, Denis
Giguère, Vincent
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
DOI: 10.1128/mcb.23.22.7947-7956.2003
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
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
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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Reduced fat mass in mice lacking orphan nuclear receptor estrogen-related receptor α.

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