Moreover, as a risk factor, dietary obesity plays important roles in the development and progression of many solid tumors, such as colorectal, breast, pancreatic and gastric cancers.[44] For example, HFD‐feeding enhances adipocytes’ secretion of microsomal triglyceride transfer protein, which induces glutathione synthesis and reduces ROS generation, and eventually promotes colorectal cancer.[45] Considering that ISG15 is upregulated in most types of cancers,[22] the ISG15‐γ‐GCL‐glutothione axis may function broadly in cancer development in addition to HCC, which warrants future study. The gene discussed is GCLC; the disease is obesity due to melanocortin 4 receptor deficiency.