ABNORMAL LIPID AND FATTY-ACID COMPOSITIONS OF KIDNEYS FROM MICE WITH POLYCYSTIC KIDNEY-DISEASE

Renal cyst development in polycystic kidney disease (PKD) involves hyperplastic growth and extensive membrane alterations, suggesting abnormal membrane composition and function. Using thin-layer and gas-liquid chromatography, we analyzed the lipid components of the kidneys from 120-day-old DBA/2FG-pcy (pcy) having PKD as compared to normal DBA/2J (DBA) mice. At sacrifice, kidneys from pcy mice were four times larger than DBA controls, indicating that extensive renal cyst growth had occurred. The ratios of cholesterol/phospholipid, choline glycerophospholipid (GPC)/ethanolamine glycerophospholipid (GPE) and alkenylacyl GPE/diacyl GPE were higher (by 25%, 41% and 72%, respectively) in the cystic kidneys, while total phosphatidylinositol (PI), GPE and cardiolipin (DPG) were lower (by 13%,23% and 27%, respectively). With respect to fatty acid compositions, there were significantly lower levels of docosahexaenoic acid (DHA, 22:6n-3) and higher levels of adrenic acid (AdA, 22:4n-6) in the phospholipids of pcy mouse kidneys. These changes were not present in serum, indicating that they were not generalized differences. Interestingly, the lower level of DHA in GPE was found to be associated with the alkenylacyl, but not the diacyl species. The fatty acids comprising the product/substrate ratio for the DELTA-4 desaturase activity were lower across all phospholipids, indicating a possible abnormality in polyunsaturated fatty acid metabolism in this model of PKD. These lipid abnormalities may influence membrane-mediated events such as receptor activation, signal transduction, ion transport and enzyme activities. The renal pathophysiologies associated with PKD may be related to the tissue lipid abnormalities described herein.