| First Author | Gantner ML | Year | 2016 |
| Journal | Endocrinology | Volume | 157 |
| Issue | 12 | Pages | 4770-4781 |
| PubMed ID | 27763777 | Mgi Jnum | J:240816 |
| Mgi Id | MGI:5896471 | Doi | 10.1210/en.2016-1767 |
| Citation | Gantner ML, et al. (2016) Complementary Roles of Estrogen-Related Receptors in Brown Adipocyte Thermogenic Function. Endocrinology 157(12):4770-4781 |
| abstractText | Brown adipose tissue (BAT) thermogenesis relies on a high abundance of mitochondria and the unique expression of the mitochondrial Uncoupling Protein 1 (UCP1), which uncouples substrate oxidation from ATP synthesis. Adrenergic stimulation of brown adipocytes activates UCP1-mediated thermogenesis; it also induces the expression of Ucp1 and other genes important for thermogenesis, thereby endowing adipocytes with higher oxidative and uncoupling capacities. Adipocyte mitochondrial biogenesis and oxidative capacity are controlled by multiple transcription factors, including the estrogen-related receptor (ERR)alpha. Whole-body ERRalpha knockout mice show decreased BAT mitochondrial content and oxidative function but normal induction of Ucp1 in response to cold. In addition to ERRalpha, brown adipocytes express ERRbeta and ERRgamma, 2 nuclear receptors that are highly similar to ERRalpha and whose function in adipocytes is largely unknown. To gain insights into the roles of all 3 ERRs, we assessed mitochondrial function and adrenergic responses in primary brown adipocytes lacking combinations of ERRs. We show that adipocytes lacking just ERRalpha, the most abundant ERR, show only mild mitochondrial defects. Adipocytes lacking ERRbeta and ERRgamma also show just mild defects. In contrast, adipocytes lacking all 3 ERRs have severe reductions in mitochondrial content and oxidative capacity. Moreover, adipocytes lacking all 3 ERRs have defects in the transcriptional and metabolic response to adrenergic stimulation, suggesting a wider role of ERRs in BAT function than previously appreciated. Our study shows that ERRs have a great capacity to compensate for each other in protecting mitochondrial function and the metabolic response to adrenergic signaling, processes vital to BAT function. |
