In this study, we showed that the DHEA combined with an HFD-induced PCOS mouse model had a significant typical PCOS phenotype, including an irregular estrus cycle, hyperandrogenism, polycystic ovarian morphology (PCOM), and metabolic syndrome manifestations such as obesity, IR, abnormal serum leptin level, impaired glucose tolerance, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD). The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.