The present study demonstrated that 50 mg/kg WL had favorable effects on diabetes and related complications (e.g., obesity, NAFLD, and hyperlipidemia) in HFD-fed mice, in a manner comparable to treatment with 250 mg/kg metformin; these effects were mediated by upregulation of AMPK-related hepatic glucose enzyme activities and lipid metabolism-related gene expression, the antioxidant defense system, and pancreatic lipid digestion enzyme modulatory activities. This evidence concerns the gene PRKAA1 and obesity disorder.