Jelenik, Tomas, Kodde, Andrea, Pesta, Dominik, Phielix, Esther, Oosting, Annemarie, Rohbeck, Elisabeth, Dewidar, Bedair, Mastrototaro, Lucia, Trenkamp, Sandra, Keijer, Jaap, van der Beek, Eline M. and Roden, Michael (2022). Dietary lipid droplet structure in postnatal life improves hepatic energy and lipid metabolism in a mouse model for postnatal programming. Pharmacol. Res., 179. LONDON: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD. ISSN 1096-1186

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Abstract

Early-life diets may have a long-lasting impact on metabolic health. This study tested the hypothesis that an early-life diet with large, phospholipid-coated lipid droplets (Concept) induces sustained improvements of hepatic mitochondrial function and metabolism. Young C57BL/6j mice were fed Concept or control (CTRL) diet from postnatal day 15 (PN15) to PN42, followed by western style (WSD) or standard rodent diet (AIN) until PN98. Measurements comprised body composition, insulin resistance (HOMA-IR), tricarboxylic acid (TCA) cycle and beta-oxidation-related hepatic oxidative capacity using high-resolution respirometry, mitochondrial dynamics, mediators of insulin resistance (diacylglycerols, DAG) or ceramides) in subcellular compartments as well as systemic oxidative stress. Concept feeding increased TCA cycle-related respiration by 33% and mitochondrial fusion protein-1 by 65% at PN42 (both p 0.05). At PN98, CTRL, but not Concept, mice developed hyperinsulinemia (CTRL/AIN 0.22 +/- 0.44 vs. CTRL/WSD 1.49 +/- 0.53 nmol/l, p 0.05 and Concept/AIN 0.20 +/- 0.38 vs. Concept/WSD 1.00 +/- 0.29 nmol/l, n.s.) and insulin resistance after WSD (CTRL/AIN 107 +/- 23 vs. CTRL/WSD 738 +/- 284, p 0.05 and Concept/AIN 109 +/- 24 vs. Concept/WSD 524 +/- 157, n.s.). WSD-induced liver weight was 18% lower in adult Concept-fed mice and beta-oxidation-related respiration was 69% higher (p 0.05; Concept/WSD vs. Concept/AIN) along with lower plasma lipid peroxides (CTRL/AIN 4.85 +/- 0.28 vs. CTRL/WSD 5.73 +/- 0.47 mu mol/l, p 0.05 and Concept/AIN 4.49 +/- 0.31 vs. Concept/WSD 4.42 +/- 0.33 mu mol/l, n.s.) and were in part protected from WSD-induced increase in hepatic cytosolic DAG C16:0/C18:1. Early-life feeding of Concept partly protected from WSD-induced insulin resistance and systemic oxidative stress, potentially via changes in specific DAG and mitochondrial function, highlighting the role of early life diets on metabolic health later in life.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Jelenik, TomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kodde, AndreaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pesta, DominikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Phielix, EstherUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Oosting, AnnemarieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rohbeck, ElisabethUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dewidar, BedairUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mastrototaro, LuciaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Trenkamp, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Keijer, JaapUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van der Beek, Eline M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Roden, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-692336
DOI: 10.1016/j.phrs.2022.106193
Journal or Publication Title: Pharmacol. Res.
Volume: 179
Date: 2022
Publisher: ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
Place of Publication: LONDON
ISSN: 1096-1186
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
NONALCOHOLIC FATTY LIVER; INSULIN-RESISTANCE; MITOCHONDRIAL-FUNCTION; PERMEABILIZED FIBERS; HOMEOSTASIS MODEL; MATERNAL OBESITY; GLOBULE-MEMBRANE; OXPHOS PROTOCOLS; GENE-EXPRESSION; ADIPOSE-TISSUEMultiple languages
Pharmacology & PharmacyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/69233

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