Effect of dietary oils and protein and cyclooxygenase-2 inhibition on disease progression and oxylipin alterations in cystic kidney disease
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Date
2019-08
Authors
Monirujjaman, Md
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Abstract
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease in humans. In animal models that are non-orthologous to ADPKD, dietary soy protein and flax oil slow disease progression, while fish oil feeding has inconsistent effects and has not been compared directly with flax oil. Therefore, weanling Pkd2WS25/-(Pkd2) mice orthologous for ADPKD were provided diets containing soy protein or casein, and soy, flax or fish oil for 13 weeks. Renal disease was assessed by histomorphometric analysis of cysts and fibrosis, and measurement of serum urea nitrogen and creatinine levels. In contrast to findings in non-orthologous models, these dietary interventions did not alter disease progression.
Oxylipins are bioactive lipid metabolites that are altered in the kidneys of models that are non-orthologous to ADPKD. In particular, oxylipins derived via the cyclooxygenase (COX) pathway are elevated. Therefore, targeted lipidomic analysis of renal oxylipins of diverse models of PKD (including the Pkd2 mouse) was performed by HPLC-MS/MS. There were differing patterns of oxylipin alterations amongst models, but COX oxylipins were consistently elevated across all types of PKD. The dietary interventions had unique effects on the kidney oxylipin profile despite not altering disease. Kidney oxylipins were higher in females for oxylipins derived via the COX pathway, and higher in males for other pathways.
Dietary high protein (HP) causes normal renal hypertrophy, worsens renal disease and reportedly increases COX oxylipins (prostanoids). However, we found that dietary HP did not alter renal prostanoids and other oxylipins in pcy mice (non-orthologous model) provided a HP diet for 13 weeks, despite having the expected physiological renal effects. On the other hand, 13 weeks of feeding a selective COX2 inhibitor (celecoxib) reduced disease in the Pkd2 mouse.
In conclusion, dietary soy protein, flax or fish oil do not alter disease in the Pkd2 mouse model of ADPKD. Kidneys from diverse PKD models display elevated prostanoids, and prostanoids also were higher in females, but diet and sex effects (or lack thereof) on oxylipins did not correlate with disease. However, the slowing of disease with celecoxib suggests that COX2 inhibitors may have therapeutic value for the treatment of ADPKD.
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Keywords
Polycystic kidney disease, Oxylipin
Citation
Md Monirujjaman, M., & Aukema, H.M. (2019). Cyclooxygenase 2 inhibition slows disease progression and improves the altered renal lipid mediator profile in the Pkd2WS25/- mouse model of autosomal dominant polycystic kidney disease. Journal of Nephrology, 32, 401-409.
Monirujjaman, M., Devassy, J. D., Yamaguchi, T., Sidhu, N., Kugita, M., Gabbs, M., et al. (2017). Distinct Bioactive Lipids Alterations in Diverse Models of Cystic Kidney Diseases. BBA: Molecular and Cell Biology of Lipids, 1862, 1562–1574.
Devassy, J. D., Yamaguchi, T., Monirujjaman, M., Gabbs, M., Ravandi, A., Zhou, J., et al. (2017). Distinct effects of dietary flax compared to fish oil, soy protein compared to casein, and sex on the renal oxylipin profile in models of polycystic kidney disease. Prostaglandins Leukot. Essent. Fatty Acids, 123, 1-13.
Yamaguchi, T., Devassy, J. D., Monirujjaman, M., Gabbs, M., Aukema, H. M. (2016). Early intervention with dietary flax and fish oil and soy protein in orthologous rodent models of human hereditary polycystic kidney disease. PLoS One, 11, e0155790.
Monirujjaman, M., Devassy, J. D., Yamaguchi, T., Sidhu, N., Kugita, M., Gabbs, M., et al. (2017). Distinct Bioactive Lipids Alterations in Diverse Models of Cystic Kidney Diseases. BBA: Molecular and Cell Biology of Lipids, 1862, 1562–1574.
Devassy, J. D., Yamaguchi, T., Monirujjaman, M., Gabbs, M., Ravandi, A., Zhou, J., et al. (2017). Distinct effects of dietary flax compared to fish oil, soy protein compared to casein, and sex on the renal oxylipin profile in models of polycystic kidney disease. Prostaglandins Leukot. Essent. Fatty Acids, 123, 1-13.
Yamaguchi, T., Devassy, J. D., Monirujjaman, M., Gabbs, M., Aukema, H. M. (2016). Early intervention with dietary flax and fish oil and soy protein in orthologous rodent models of human hereditary polycystic kidney disease. PLoS One, 11, e0155790.