These β-cell adaptations to obesity involve biochemical pathways triggered by higher levels of glucose, amino acids, and free fatty acids that increase glucose metabolism and mitochondrial lipid oxidation while increasing insulin synthesis and expression of transcription factors and β-cell differentiation markers, including MafA, Pdx1, NeuroD1, Nkx6.1, and Pax6 (22). The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.