| First Author | Brown EL | Year | 2018 |
| Journal | iScience | Volume | 2 |
| Pages | 221-237 | PubMed ID | 29888756 |
| Mgi Jnum | J:339558 | Mgi Id | MGI:7520640 |
| Doi | 10.1016/j.isci.2018.03.005 | Citation | Brown EL, et al. (2018) Estrogen-Related Receptors Mediate the Adaptive Response of Brown Adipose Tissue to Adrenergic Stimulation. iScience 2:221-237 |
| abstractText | Adrenergic stimulation of brown adipose tissue (BAT) induces acute and long-term responses. The acute adrenergic response activates thermogenesis by uncoupling oxidative phosphorylation and enabling increased substrate oxidation. Long-term, adrenergic signaling remodels BAT, inducing adaptive transcriptional changes that expand thermogenic capacity. Here, we show that the estrogen-related receptors alpha and gamma (ERRalpha, ERRgamma) are collectively critical effectors of adrenergically stimulated transcriptional reprogramming of BAT. Mice lacking adipose ERRs (ERRalphagamma(Ad-/-)) have reduced oxidative and thermogenic capacity and rapidly become hypothermic when exposed to cold. ERRalphagamma(Ad-/-) mice treated long term with a beta(3)-adrenergic agonist fail to expand oxidative or thermogenic capacity and do not increase energy expenditure in response to norepinephrine (NE). Furthermore, ERRalphagamma(Ad-/-) mice fed a high-fat diet do not lose weight or show improved glucose tolerance when dosed with beta(3)-adrenergic agonists. The molecular basis of these defects is the finding that ERRs mediate the bulk of the transcriptional response to adrenergic stimulation. |
