Various genetic and environmental factors can lead to the accumulation of unfolded proteins in the lumen of the ER, causing ERS.38, 39 Eukaryotic cells have a system known as the unfolded protein response (UPR) to attenuate ERS, which is composed of three main sensors: PKR‐like ER kinase (PERK), inositol requires enzyme 1 (IRE1) and activating transcription factor 6 (ATF6).40 Furthermore, Hoxa5 promotes browning of white fat by inhibiting LPS‐induced inflammation and thus plays a positive role in fat metabolism.26 However, the role of Hoxa5 in obesity‐induced ERS is still unknown. This evidence concerns the gene ERN1 and obesity due to melanocortin 4 receptor deficiency.