2001). In vivo studies have revealed that some of the orphan NR regulates the pathophysiology of obesity and insulin resistance (for a review see Pearen and Muscat (2012)). The orphan nuclear factor retinoid‐related orphan receptor α (RORα), for example, is involved in several processes that are deregulated in pathologically expanding adipose tissue such as inflammation, adipogenesis, circadian rhythms, and lipid homeostasis (see Cook et al. 2015 for a review). Here, RORA is linked to obesity due to melanocortin 4 receptor deficiency.