ERRγ enhances UCP1 expression and fatty acid oxidation in brown adipocytes

Authors


  • Disclosure: The authors declare no conflict of interest directly related to the data presented here.

  • Funding agencies: We appreciate the gift of valuable reagents from Bruce M. Spiegelman (Harvard Medical School, Dana Farber Cancer Institute, Boston), C. Ronald Kahn (Joslin Diabetes Center, Harvard Medical School, Boston), Hueng-Sik Choi (Chonnam National University, Gwangju, Korea), Piia Aarnisalo (University of Helsinki, Helsinki University Central Hospital, Finland), and Amgen (California). This work was supported by grants to J.B.H. from the EU FP7 project DIABAT (HEALTH-F2-2011-278373), Danish Medical Research Council, the Novo Nordisk Foundation, the Carlsberg Foundation, the Aase and Ejnar Danielsen Foundation, the Augustinus Foundation, the Hartmann Brothers' Foundation and the Beckett Foundation, to B.Q. from the Danish Strategic Research Council (09-067124 and 09-059921) and the European Union through the network of excellence, BioSim (contract no. LDHB-CT-2004-005137) and to J.N. from the Swedish Science Council.

Abstract

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.

Ancillary