Elevated n-3/n-6 PUFA ratio in early life diet reverses adverse intrauterine kidney programming in female rats
Voggel J, Fink G, Zelck M, Wohlfarth M, Post JM, Bindila L, Rauh M, Amann KU, Alcazar MAA, Doetsch J, Nuesken KD, Nuesken E (2022)
Publication Type: Journal article
Publication year: 2022
Journal
Book Volume: 63
Journal Issue: 11
DOI: 10.1016/j.jlr.2022.100283
Abstract
Intrauterine growth restriction (IUGR) predisposes to chronic kidney disease via activation of proinflammatory pathways, and omega-3 PUFAs (n-3 PUFAs) have anti-inflammatory properties. In female rats, we investigated 1) how an elevated di-etary 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 pro-tein signatures expected in IUGR kidneys. IUGR was induced by bilateral uterine vessel ligation or intra-uterine stress through sham operation 3.5 days before term. Control (C) offspring were born after uncom-promised pregnancy. On postnatal (P) days P2-P39, rats were fed control (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 pro-teomics, as well as histology (P39) were studied. We found that the intervention diet tripled PL-DHA content (PC 40:6; P < 0.01) and lowered both PL-AA content (PC 38:4 and lyso-phosphatidylcholine 20:4; P < 0.05) and AA metabolites (HETEs, dihydrox-yeicosatrienoic acids, and epoxyeicosatrienoic acids) to 25% in all offspring groups. After ligation, 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 miti-gating adverse IUGR signatures. In conclusion, an elevated n-3/n-6 PUFA ratio in early diet strongly reduces proinflammatory PLs and mediators while increasing DHA-containing PLs regardless of prior intrauterine conditions. Counteracting a proin-flammatory 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.
Authors with CRIS profile
Manfred Rauh
Department of Paediatrics and Adolescent Medicine
Kerstin Ute Amann
Professur für Nephropathologie
Involved external institutions
Germany (DE)How to cite
APA:
Voggel, J., Fink, G., Zelck, M., Wohlfarth, M., Post, J.M., Bindila, L.,... Nuesken, E. (2022). Elevated n-3/n-6 PUFA ratio in early life diet reverses adverse intrauterine kidney programming in female rats. Journal of Lipid Research, 63(11). https://doi.org/10.1016/j.jlr.2022.100283
MLA:
Voggel, Jenny, et al. "Elevated n-3/n-6 PUFA ratio in early life diet reverses adverse intrauterine kidney programming in female rats." Journal of Lipid Research 63.11 (2022).
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