INS and obesity due to melanocortin 4 receptor deficiency: These studies suggested that adipose tissue-derived Nrg4 could exert positive effects on obesity associated metabolic disturbances (Wang et al., 2014; Ma et al., 2016; Chen et al., 2017; Guo et al., 2017), improving glucose tolerance and insulin sensitivity and attenuating adipose tissue and liver inflammation (Wang et al., 2014; Ma et al., 2016; Chen et al., 2017; Guo et al., 2017).