Universität zu Köln

Voggel, Jenny, Fink, Gregor, Zelck, Magdalena, Wohlfarth, Maria, Post, Julia M., Bindila, Laura, Rauh, Manfred, Amann, Kerstin, Alcazar, Miguel A. Alejandre, Doetsch, Joerg, Nuesken, Kai-Dietrich and Nuesken, Eva (2022). Elevated n-3/n-6 PUFA ratio in early life diet reverses adverse intrauterine kidney programming in female rats. J. Lipid Res., 63 (11). AMSTERDAM: ELSEVIER. ISSN 1539-7262

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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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Voggel, Jenny UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, Gregor UNSPECIFIED UNSPECIFIED UNSPECIFIED Zelck, Magdalena UNSPECIFIED UNSPECIFIED UNSPECIFIED Wohlfarth, Maria UNSPECIFIED UNSPECIFIED UNSPECIFIED Post, Julia M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bindila, Laura UNSPECIFIED UNSPECIFIED UNSPECIFIED Rauh, Manfred UNSPECIFIED UNSPECIFIED UNSPECIFIED Amann, Kerstin UNSPECIFIED UNSPECIFIED UNSPECIFIED Alcazar, Miguel A. Alejandre UNSPECIFIED UNSPECIFIED UNSPECIFIED Doetsch, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuesken, Kai-Dietrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuesken, Eva UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-678824
DOI:	10.1016/j.jlr.2022.100283
Journal or Publication Title:	J. Lipid Res.
Volume:	63
Number:	11
Date:	2022
Publisher:	ELSEVIER
Place of Publication:	AMSTERDAM
ISSN:	1539-7262
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language LOW-BIRTH-WEIGHT; FATTY-ACID COMPOSITION; UTERINE ARTERY LIGATION; DOCOSAHEXAENOIC ACID; PROSTAGLANDIN SYNTHESIS; GROWTH RESTRICTION; ARACHIDONIC-ACID; MESANGIOPROLIFERATIVE GLOMERULONEPHRITIS; UTEROPLACENTAL INSUFFICIENCY; THROMBOTIC MICROANGIOPATHY Multiple languages Biochemistry & Molecular Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/67882