BACKGROUND/AIMS: Previously, we demonstrated that soy protein ameliorates the diabetic phenotype in several rodent models of obesity and metabolic syndrome (MS). This study was designed to further elucidate factors related to adiposity, glycemic control, and renal function in male Zucker Diabetic Fatty (ZDF/Lepr(fa)) rats.

METHODS: Animals were randomly assigned to one of four diets: control, casein (C); low isoflavone (LIS) soy protein; high isoflavone (HIS) soy protein, or casein + rosiglitazone (CR) for 11 weeks. At sacrifice, physiological, biochemical, and molecular parameters were determined.

RESULTS: Body weight and total adiposity were higher in LIS and CR diet groups despite lower food intake. Additionally, these animals exhibited differential regulation of adipose-specific proteins (PPAR-gamma and GLUT4) and enzyme activity (FAS and GPDH). HIS-fed animals had reduced total and liver adiposity. Glycemic control was prolonged in both soy-based and rosiglitazone (RGZ) groups. Renal dysfunction was significantly reduced in soy-fed and RGZ-treated rodents as demonstrated by lower levels of proteinuria and dilated tubules with proteinaceous casts.

CONCLUSION: Collectively, these data provide evidence that soy protein with low or high isoflavone content may have therapeutic significance in reducing severity of diabetes, MS, and renal disease as demonstrated in this preclinical model.