Gluconeogenesis disorder is the most typical feature of insulin resistance in which HNF-4α synergizes with PGC-1α, FOXO1 and other key enzymes to induce gluconeogenesis [20], and Leptin regulates the AMPK pathway by inhibiting HNF-4α and promoting SIRT1 expression (21). The gene discussed is HNF4A; the disease is Insulin resistance.