This is exemplified in two independent studies showing that β-cell compensation for dietary insulin resistance and obesity is regulated by the nuclear factor erythroid 2-related factor (NRF2), a basic leucine-zipper transcription factor that acts through its key targets including superoxide dismutase, catalase, and glutathione peroxidase 1 to defend cells against oxidative stress (68, 69, 70). The gene discussed is NFE2L2; the disease is obesity due to melanocortin 4 receptor deficiency.