ERN1 and obesity due to melanocortin 4 receptor deficiency: For example, adipocyte-specific knockout of IRE1α was shown to promote brown adipose tissue (BAT) activation and browning of white adipose tissue (WAT) and alleviate diet-induced obesity and insulin resistance by suppressing its RNase-mediated degradation of the mRNA of thermogenic gene PGC1α and hence elevating UCP1 level (Chen, Wu et al. 2022).