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. This evidence concerns the gene FGF21 and obesity due to melanocortin 4 receptor deficiency.