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.

Dietary Flax Oil During Pregnancy and Lactation Retards Disease Progression in Rat Offspring With Inherited Kidney Disease

“…The beneficial effects of flax oil given maternally are consistent with previous studies that reported amelioration of renal injury when flax oil intervention was introduced in the adult or postweaning stages (6,7,19). In cystic kidney diseases, recent evidence suggests that cyst expansion precedes the changes in function and is associated with the initiation of inflammation, fibrosis and other secondary changes (24).…”

“…Flax oil (FO) was a generous gift from Bioriginal Food and Science Corporation (Saskatoon, SK). Diets were based on the AIN93G guidelines for rodent diets for optimal growth and adequate nutrition (19,20). Hence the diets were identical (including calorie, carbohydrate, protein, mineral and vitamin content) except for the fat source.…”

“…The formalin-fixed left kidney was embedded in paraffin, sectioned at 5 m and was processed using our previously described methods for histologic and immunohistochemical analyses (7,19). Transverse tissue sections (including cortex, medulla and papilla) were stained with hematoxylin and eosin for cyst area measurement and those for quantitative analysis of fibrosis with Sirius red (in adaptation of Masson's trichrome stain) which permits image analysis measurement using a standard incandescent microscope light source.…”

“…After being captured using a SPOT junior CCD camera by random stage movement through the sections, images were analyzed using the Image Pro version 4.5 package (Media Cybernetics, Silver Spring, MD) as described previously (7,19). An average of 25 measurements starting from a random field of tissue section from kidney cross-sections were collected for all histomorphometric analyses.…”

“…The portion of tissue section occupied by tubular lumen or cyst was determined for cyst area measurements. Renal interstitial fibrosis and oxidant injury were measured by densitometry, while the number of cells stained positive for PCNA as well as macrophages were counted using the Image Pro version 4.5 package (Media Cybernetics, Silver Spring, MD) as described previously (7,19). Renal cyst area measurements were expressed relative to kidney weight-to-body weight ratios.…”