NRF1 and obesity due to melanocortin 4 receptor deficiency: The BAT thermogenic activation following cold adaptation or treatment with CL316243, an adipocyte-specific β3-adrenergic agonist 376 at thermoneutrality de facto requires an Nrf1-mediated increased activity of proteasomes to fulfill its metabolic potential, but such proteasomal activity is impaired in obesity.