ALTERED RENAL DIACYLGLYCEROL MASS AND FATTY-ACID COMPOSITIONS IN MURINE POLYCYSTIC KIDNEY-DISEASE - DIETARY-EFFECTS

The mass amounts and fatty acid compositions of the second messenger, diacylglycerol, have been shown to be altered in several disease states and in transformed cells. In the present study, the mass amounts and fatty acid compositions of renal diacylglycerol were determined in a mouse model of polycystic kidney disease. Kidney diacylglycerol (nmol/100 nmol phospholipid) was elevated by 21% in diseased mice compared to normal controls. Diseased kidneys were also characterized by higher levels of stearic (18:0) and arachidonic (20:4n-6) acids and lower levels of eicosenoic (20:1) and docosapentaenoic (22:5n-6) acids in the diacylglycerol fraction. Furthermore, the level and fatty acid compositions of kidney diacylglycerol in the mice with polycystic kidney disease were modified by altering dietary protein levels and lipid type. Compared with high protein diets, low protein diets were associated with both higher renal diacylglycerol levels (overall by 31%), and a retardation of renal cystic disease progression. Substituting dietary sunflowerseed oil with fish oil resulted in markedly lower levels of n-6 fatty acids and higher levels of n-3 fatty acids in kidney diacylglycerol. It remains to be determined what effect these changes in diacylglycerol level and type may have on protein kinase C-mediated events associated with biochemical defects found in polycystic kidney disease. These findings raise the possibility that diet-induced alterations of diacylglycerol mass and fatty acid compositions in vivo could be utilized to modify intracellular signalling events that accompany certain pathophysiologic conditions.