However, these findings implied possible opposite roles for NRF3 in obesity-induced cancer development (Figure 4): NRF3-SREBP2-HMGCR and the following NRF3-GGPS1-GGPS axes regulate lipid homeostasis and confer resistance to obesity through lipogenesis inhibition, while the NRF3-POMP-20S proteasome and NRF3-CPEB3-NRF1 axes regulate protein homeostasis and confer ubiquitin-independent protein degradation for continuous cancer cell growth. Here, HMGCR is linked to obesity due to melanocortin 4 receptor deficiency.