Intrauterine growth restriction (IUGR) predisposes to chronic kidney disease (CKD) via activation of pro-inflammatory pathways, and omega-3 polyunsaturated fatty acids (n-3 PUFAs) have anti-inflammatory properties. In female rats, we investigated (1) how an elevated dietary n-3/n-6 PUFA ratio (1:1) during postnatal kidney development modifies kidney phospholipid (PL) and arachidonic acid (AA) metabolite content and (2) whether the diet counteracts adverse molecular protein signatures expected in IUGR kidneys. IUGR was induced by bilateral uterine vessel ligation (LIG) or intrauterine stress (IUS) through sham operation 3.5 days before term. Control (C) offspring were born after uncompromised pregnancy. On postnatal (P) days P2-P39, rats were fed control (CONTR; n-3/n-6 PUFA ratio 1:20) or n-3 PUFA intervention diet (N3PUFA; ratio 1:1). Plasma parameters (P33), kidney cortex lipidomics and proteomics as well as histology (P39) were studied. We found that the intervention diet tripled PL-docosahexaenoic acid (DHA) content (PC40:6; p<0.01) and lowered both PL-AA content (PC38:4 and LPC20:4; p<0.05) and AA metabolites (HETEs, DiHETrEs, EETs) to 25% in all offspring groups. After LIG, our network analysis of differentially expressed proteins identified an adverse molecular signature indicating inflammation and hypercoagulability. N3PUFA diet reversed 61 protein alterations (p<0.05), thus mitigating adverse IUGR signatures. In conclusion, an elevated n-3/n-6 PUFA ratio in early diet strongly reduces pro-inflammatory PLs and mediators while increasing DHA-containing PLs regardless of prior intrauterine conditions. Counteracting a pro-inflammatory, hypercoagulable protein signature in young adult IUGR individuals through early diet intervention may be a feasible strategy to prevent developmentally programmed kidney damage in later life. Arachidonic acid, developmental origins of health and disease, eicosanoids, chronic kidney disease, lipidomics, nutrition, omega-3 fatty acids, perinatal programming, placental insufficiency, proteomics.
- Voggel, J.
- Fink, G.
- Zelck, M.
- Wohlfarth, M.
- Post, J. M.
- Bindila, L.
- Rauh, M.
- Amann, K.
- Alejandre Alcázar, M. A.
- Dötsch, J.
- Nüsken, K. D.
- Nüsken, E.
