linoleic-acid and Polycystic-Kidney-Diseases

Dietary n-3 fatty acids generally attenuate elevated cyclooxygenase-2 (COX-2) levels in disease states. However, models of renal cystic disease (RCD) exhibit reduced renal COX-2 expression. Therefore, the in vivo regulation of COX-2 expression by dietary n-3 fatty acids was examined. In archived tissues from dietary studies, COX-2 protein and gene expression was up-regulated in diseased pcy mouse and Han:SPRD-cy rat kidneys when given diets containing eicosapentaenoic acid (EPA) and/or docosahexaenoic acid (DHA), but not those containing alpha-linolenic acid (ALA), compared to control diets with linoleic acid (LA). The presence of disease was necessary to elicit these effects as COX-2 expression was unaltered by diet in normal kidneys. The effects were specific for COX-2, since COX-1 levels were unaltered by these dietary manipulations in either model. Thus, in RCD, diets containing EPA and DHA but not ALA appear to specifically up-regulate renal COX-2 gene and protein levels in vivo.

Topics: Animals; Cyclooxygenase 2; Dietary Fats; Disease Models, Animal; Fatty Acids, Omega-3; Gene Expression Regulation, Enzymologic; Linoleic Acid; Male; Mice; Mice, Inbred Strains; Polycystic Kidney Diseases; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Weaning

Conjugated linoleic acid (CLA) describes positional isomers of linoleic acid (LA). Experimental health benefits of CLA include amelioration of malignancy and inflammatory disease and reduction of adiposity. The Han:SPRD-cy rat model of polycystic kidney disease (PKD) features prominent renal interstitial inflammation and fibrosis that is amenable to dietary modification. We studied CLA supplementation in the modification of inflammatory outcomes in the Han:SPRD-cy rat.. Male offspring of Han:SPRD-cy heterozygotes were fed diets, using corn oil or corn oil with a CLA enriched oil (1% of diet by weight as CLA). After 8 weeks, measurements included renal function and morphometry, ex vivo release of renal prostaglandin E2 (PGE2), and renal and hepatic tissue fatty acid profiles.. Urine creatinine was significantly higher in PKD animals fed CLA (P = 0.004), but differences in serum creatinine and creatinine clearance did not quite reach significance in PKD animals. CLA feeding reduced interstitial inflammation (P < 0.001), fibrosis (P = 0.03), and renal PGE2 release (P = 0.02). Cystic change and oxidized low-density lipoprotein (LDL) staining did not change significantly. CLA feeding produced increased renal and hepatic CLA isomers. Hepatic, but not renal, LA proportion was reduced on the CLA diet. The renal proportion of the PGE2 precursor, arachidonic acid (AA), was not changed by diet, but hepatic AA proportion increased significantly with CLA feeding (P= 0.009).. CLA reduces renal production of PGE2, without reduced availability of the precursor fatty acid, AA. Short-term feeding of CLA to Han:SPRD-cy rats also has significant renal anti-inflammatory and antifibrotic effects. As inflammation and fibrosis are important components of the progression of chronic renal injury, CLA may be a useful agent in dietary amelioration of renal disease.

Topics: Animals; Arachidonic Acid; Creatinine; Diet; Dinoprostone; Fibrosis; Isomerism; Kidney; Linoleic Acid; Linoleic Acids, Conjugated; Liver; Male; Polycystic Kidney Diseases; Rats; Rats, Inbred Strains