Effect of dietary soy protein and oils containing omega-3 fatty acids on disease and renal oxylipins in polycystic kidney disease
Polycystic kidney disease (PKD) is the most common genetic renal disease for which no curative treatment is currently available. Oxylipins are bioactive lipids formed from polyunsaturated fatty acids (PUFA), having roles in proliferation and inflammation, processes involved in PKD progression. Oxylipin alterations have been reported in non-orthologous models of PKD. In these models, dietary soy protein and n-3 PUFA have shown benefits. However, recent studies in an orthologous model and humans have yielded conflicting results. To examine whether benefit of dietary treatments in non-orthologous models are replicated in orthologous models, and to investigate the role of oxylipins, four independent studies were conducted using PCK rats, Pkd2WS25/-(Pkd2) mice and Mx1Cre+Pkd1flox/flox(Pkd1) mice. Animals were given either casein or soy protein and one of soy, flax or fish oil in the diet. Generally, fish oil yielded no beneficial effects on disease but resulted in enlarged kidneys in all three models and higher kidney water content in PCK rats and Pkd2 mice. Flax oil resulted in lower water content in Pkd1 mice kidneys, but higher water content, size and cyst in PCK rat kidneys. Dietary soy protein improved proteinuria and urine pH, only in PCK rats. Targeted lipidomics was used to screen for over 150 oxylipins of which 50-55 were detected in each model. Cyclooxygenase derived oxylipins were consistently higher in diseased compared to normal animals and cytochrome P450 epoxygenase derived oxylipins were lower only in PCK rats. Fish oil was more effective than flax oil in reducing n-6 oxylipins. Fish oil also resulted in the highest levels of EPA and DHA oxylipins, whereas flax oil had the highest ALA oxylipins. Soy protein compared to casein resulted in higher LA oxylipins. AA oxylipins were higher in females compared to males, while oxylipins from other PUFA were either higher in males or unaffected. Therefore, in contrast to studies in non-orthologous models, these studies do not support dietary advice to increase soy protein or oils enriched in n-3 PUFA in early PKD. Disease associated oxylipin alterations, unique effects of soy protein on LA and sex on AA oxylipins are novel findings that demand further research.