Well-established NAFLD/NASH mouse models successfully induce fibrosis, but struggle to recapitulate the full complexity of human disease, which often presents signs of metabolic syndrome (MS). In order to develop a more translatable NASH model that presents with MS, we fed mice a high-fat, cholesterol-rich western-diet (WD), and supplemented drinking water with fructose. A WD in combination with traditional methods to induce NASH exacerbates and facilitates the full spectrum of clinical presentations seen with human NAFLD/NASH disease, including obesity, impaired glucose tolerance and hepatic steatosis.