Abnormal lipid and fatty acid compositions of kidneys from mice with polycystic kidney disease

Abstract

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.

Dietary flax oil reduces renal injury, oxidized LDL content, and tissue n−6/n−3 FA ratio in experimental polycystic kidney disease

“…DHA, but not EPA, in vivo reduces mesangial proliferation and has been proposed as a potential explanation of the apparent benefit of dietary fish oil in immunoglobulin A nephropathy (29). Expression of PKD was associated with a reduction in DHA in this study, a phenomenon also observed in the pcy mouse (30). In the 5/6-nephrectomy rat, Ingram et al both flax diets (9).…”

The study on serum and urine of renal interstitial fibrosis rats induced by unilateral ureteral obstruction based on metabonomics and network analysis methods

“…Docosapentaenoic acid (C16513) is an intermediary between eicosapentaenoic acid (20:5, ω-3) and docosahexaenoic acid (22:6, ω-3) that lowers plasma cholesterol [37]. Docosapentaenoic acid deficiency in experimental animals causes lesions because of faulty cellular membranes, as well as sudden failure to grow of kidney and connective tissues [38]. Eicosapentaenoic acid (C06428) is an important polyunsaturated fatty acid that prevents platelet aggregation, expands the blood vessels, and reduces ischemia and hypoxia in renal tissue [39].…”

Electrospray/Tandem Mass Spectrometry for Quantitative Analysis of Lipid Remodeling in Essential Fatty Acid Deficient Mice

“…The enrichment of adrenic acid and docosapentaenoic acid in the CE and phospholipid lipid species of peritoneal cells (primarily macrophages) had not been reported previously. Adrenic acid has been reported to be enriched in mouse kidney (27), human platelets (28), and rat pituitary (29,30). Leukocytes have been described as possessing fatty acid elongase, but not fatty acid ⌬6 or ⌬5 desaturase activities (31)(32)(33)(34).…”