The connection between PPAR-γ, PPAR-α, and serum levels of FGF-21 in the context of metabolic disorders such as type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), obesity, poly-cystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), cardiac disease, and dyslipidemia arises from their roles in regulating glucose and lipid metabolism, insulin sensitivity, inflammation, and oxidative stress. The gene discussed is INS; the disease is obesity due to melanocortin 4 receptor deficiency.