Brown adipose tissue (BAT) needs to dissipate vast amounts ofintracellular and circulating nutrients to sustain its exceptional oxidativemetabolic activity for thermogenesis, and in doing so BAT activity exertsbeneficial metabolic effects on obesity, insulin resistance andatherosclerosis. Identifying factors that protect adipocytes from metabolicstress during the adaptation to cold and obesity may hold great potentialtowards therapeutic approaches for metabolic diseases. As the dramaticmetabolic changes in BAT not only involve dissipation of energy-rich nutrientsbut also the de novo synthesis of new proteins, lipids and cellular organelles,adaptation to cold or excess nutrients might require special mechanisms forincreased quality control of these metabolic processes. While the endoplasmic reticulum (ER) is a critical organelle formetabolic homeostasis, the mechanisms that mediate adaptation of the ER inadipocytes are unclear. We will discuss novel insight into the molecularmechanisms guarding brown fat againstmetabolic stress in cold and obesity. In particular, we will focus on theunfolded protein response and ER-associated protein degradation as the mostcritical pathways by which the ER responds to increased metabolic demand anddiscuss how these are engaged in brown adipocytes. In this context, we haveidentified Nfe2l1, also known as Nrf1, as a novel regulator of ER homeostasisin BAT. Using in vitro systems and mouse models we will address thephysiological, pathological and translational relevance of Nfe2l1/Nrf1 for the adaptationof BAT to cold and obesity.