The development of type II diabetes mellitus (T2DM) is strongly associated with consuming a western diet, high in sugars and fats. Metabolites from both dietary fats and carbohydrates can regulate each other through transcriptional regulators like carbohydrate response element-binding protein (ChREBP) and sterol regulatory element-binding protein-1c (SREBP-1c), complicating the potential mechanisms driving the development of T2D. Both excess sugar and excess fat consumption can drive obesity independently, but combinatorial feeding studies show that fructose, but not glucose, exaggerates liver stenosis and ectopic fat deposition caused by dietary fat.