HBEGF and obesity due to melanocortin 4 receptor deficiency: It releases and activates numerous biologically significant ligands, including tumor necrosis factor (TNF), epidermal growth factor (EGF), transforming growth factor-a (TGF-a), amphiregulin, and HB-EGF, which were found to be associated with the progression of distinct diseases (e.g., liver fibrosis, obesity, and asthma) and cancers (Kveiborg et al., 2005; Rocks et al., 2008; Roy and Moses, 2012; Nyren-Erickson et al., 2013).