Prevention of obesity-linked renal disease: age-dependent effects of dietary food restriction.

BACKGROUND: Hyperphagic obese Zucker rats develop glomerular injury and die of renal disease, an outcome prevented by food restriction at an early age. We examined the effects of food restriction imposed at different ages on systemic, renal hemodynamic, and hormonal changes to gain insight into the mechanisms of obesity-linked glomerular injury. METHODS: At 6 weeks of age obese Zucker rats were either fed ad libitum or were restricted in food intake at various ages (6, 12, 26, or 50 weeks) to that consumed by lean Zucker rats (14 g/day). Every four weeks 24-hour urine collections, blood pressure, and venous blood samples were obtained until the end of study (60 weeks). RESULTS: Food restriction at 6 or 12 weeks of age prevented glomerular injury and hypertrophy and delayed the development of hypertension, hypercholesterolemia, and hyperinsulinemia. Food restriction at 26 weeks of age reduced proteinuria, while restriction at 50 weeks prevented further increases in proteinuria without altering pre-existing hypercholesterolemia, hypertension, or hyperinsulinemia. Hypertriglyceridemia and glomerular hyperfiltration in the obese animals were reversed at any age by food restriction. Plasma leptin levels were elevated in all obese groups. CONCLUSIONS: (1) Early food restriction provided the greatest metabolic and renal benefits; (2) glomerular injury correlated with hyperphagia-induced hyperfiltration and hypertriglyceridemia and both were prevented by food restriction; (3) hypercholesterolemia was due to an increase in LDL and/or VLDL cholesterol; and (4) leptin does not directly contribute to glomerular injury in the obese Zucker rat.

Protective effects of a soy diet in preventing obesity-linked renal disease.

BACKGROUND: Hypertension, hyperlipidemia, hyperfiltration, hyperinsulinemia, glomerular hypertrophy, and ultimately glomerular injury and renal failure are associated with obesity in the Zucker rat. Evidence from other laboratories suggests that soy protein might offer renal protection. METHODS: At five weeks of age obese rats were placed on diets containing either soy or casein as a protein source and studied until 24 weeks of age. At six weeks of age and every four weeks thereafter, 24-hour urine collections were obtained along with measurements of systolic blood pressure (tail cuff) and blood from the tail vein. At the end of the study the kidneys were fixed and sectioned for histology. RESULTS: Both groups gained weight and developed systemic hypertension and hyperinsulinemia at the same rate. Glomerular filtration rate (creatinine clearance) also was similar between groups throughout the study and both groups developed glomerular hypertrophy to the same extent. The development of hypertriglyceridemia was actually accelerated in the soy-fed rats compared to the casein-fed animals. The soy diet, however, virtually completely prevented the development of hypercholesterolemia, primarily low-density lipoprotein (LDL) and/or very low-density lipoprotein (VLDL) cholesterol, and slowed the development of proteinuria and glomerular injury. CONCLUSIONS: The data suggest that an important determinant of the protective effects of soy was related to the prevention of hypercholesterolemia in this model. Other unmeasured differences between groups, such as differences in glomerular capillary blood pressure or the effects of the antioxidant properties of soy components also may have contributed to the protective effects of soy.