ERRγ enhances UCP1 expression and fatty acid oxidation in brown adipocytes

• Published in: Obesity (Silver Spring, Md.) Md.), 2013-03, Vol.21 (3), p.516-524
• Main Authors: Dixen, Karen, Basse, Astrid L., Murholm, Maria, Isidor, Marie S., Hansen, Lillian H. L., Petersen, M. Christine H., Madsen, Lise, Petrovic, Natasa, Nedergaard, Jan, Quistorff, Bjørn, Hansen, Jacob B.
• Format: Article
• Language: English
• Subjects: Adipocytes, Brown - metabolism; Adipocytes, White - metabolism; Adipogenesis; Adipose Tissue, White - metabolism; Animals; Cell Differentiation; Cells, Cultured; DNA Copy Number Variations; DNA, Mitochondrial - genetics; DNA, Mitochondrial - isolation & purification; Energy Metabolism; Female; Ion Channels - genetics; Ion Channels - metabolism; L-Lactate Dehydrogenase - genetics; L-Lactate Dehydrogenase - metabolism; Lipid Metabolism; Lipolysis - physiology; Mice; Mice, Inbred C57BL; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Oxidation-Reduction; Palmitoylcarnitine - metabolism; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Rats; Rats, Wistar; Receptors, Estrogen - genetics; Receptors, Estrogen - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Trans-Activators - genetics; Trans-Activators - metabolism; Transcription Factors - genetics; Transcription Factors - metabolism; Uncoupling Protein 1
• ISSN: 1930-7381; 1930-739X; 1930-739X
• DOI: 10.1002/oby.20067

Objective: Estrogen‐related receptors (ERRs) are important regulators of energy metabolism. Here we investigated the hypothesis that ERRγ impacts on differentiation and function of brown adipocytes. Design and Methods: We characterize the expression of ERRγ in adipose tissues and cell models and investigate the effects of modulating ERR? activity on UCP1 gene expression and metabolic features of brown and white adipocytes. Results: ERRγ was preferentially expressed in brown compared to white fat depots, and ERRγ was induced during cold‐induced browning of subcutaneous white adipose tissue and brown adipogenesis. Overexpression of ERRγ positively regulated uncoupling protein 1 (UCP1) expression levels during brown adipogenesis. This ERRγ‐induced augmentation of UCP1 expression was independent of the presence of peroxisome proliferator‐activated receptor coactivator‐1 (PGC‐1α) but was associated with increased rates of fatty acid oxidation in adrenergically stimulated cells. ERR? did not influence mitochondrial biogenesis, and its reduced expression in white adipocytes could not explain their low expression level of UCP1. Conclusions: Through its augmenting effect on expression of UCP1, ERRγ may physiologically be involved in increasing the potential for energy expenditure in brown adipocytes, a function that is becoming of therapeutic interest.