Modulation of renal injury in pcy mice by dietary fat containing n-3 fatty acids depends on the level and type of fat.

Abstract

Low-fat diets and diets containing n-3 fatty acids (FA) slow the progression of renal injury in the male Han:Sprague-Dawley (SPRD)-cy rat model of polycystic kidney disease. To determine whether these dietary fat effects are similar in females and in another model of renal cystic disease, in this study we used both male and female pcy mice to examine the effects of fat level and type on disease progression. Adult pcy mice were fed 4, 10, or 20 g soybean oil/100 g diet for 130 d in study 1. In study 2, weanling pcy mice were fed high or low levels of fat rich in 18:2n-6 (corn oil, CO), 18:3n-3 (flaxseed oil/CO 4:1 g/g, FO), or 22:6n-3 (algal oil/CO 4:1 g/g, DO) for 8 wk. In adult pcy mice, low- compared with high-fat diets lowered kidney weights (2.4 +/- 0.2 vs. 3.1 +/- 0.2 g/100 g body weight, P = 0.006) and serum urea nitrogen (SUN) (9.6 +/- 0.6 vs. 11.9 +/- 0.6 mmol/L, P = 0.009), whereas in young pcy mice it reduced renal fibrosis volumes (0.44 +/- 0.04 vs. 0.62 +/- 0.04 mL/kg body weight, P < 0.0001). FO feeding in young pcy mice mitigated the detrimental effects of high fat on fibrosis while not altering kidney size, function, and oxidative damage when compared with the CO-fed mice. In contrast, DO- compared with CO-fed mice had higher kidney weights (2.64 +/- 0.07 vs. 2.24 +/- 0.08 g/100 g body weight, P = 0.005), SUN (9.4 +/- 0.57 vs. 7.0 +/- 0.62 mmol/L, P < 0.0001), and cyst volumes (7.9 +/- 0.28 vs. 6.2 +/- 0.30 mL/kg body weight, P < 0.0001) and similar levels of oxidative damage and fibrosis. The FA compositions of the diets were reflected in the kidneys: 18:2n-6, 18:3n-3, and 22:6n-3 were the highest in the CO, FO, and DO diets, respectively. Dietary effects on kidney disease progression were similar in males and females. A low-fat diet slows progression of renal injury in male and female pcy mice, consistent with findings in the male Han:SPRD-cy rat. Dietary fat type also influenced renal injury, with flaxseed oil diets rich in 18:3n-3 slowing early fibrosis progression compared with diets rich in 18:2n-6 or in 22:6n-3.