Jelenik 2022 Pharmacol Res

Jelenik T, Kodde A, Pesta D, Phielix E, Oosting A, Rohbeck E, Dewidar B, Mastrototaro L, Trenkamp S, Keijer J, van der Beek EM, Roden M (2022) Dietary lipid droplet structure in postnatal life improves hepatic energy and lipid metabolism in a mouse model for postnatal programming. https://doi.org/10.1016/j.phrs.2022.106193

» Pharmacol Res 179:106193. PMID: 35358682 Open Access

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, Roden Michael (2022) Pharmacol Res

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 β-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 β-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 µmol/l, p 0.05 and Concept/AIN 4.49 ± 0.31 vs. Concept/WSD 4.42 ± 0.33 µmol/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. • Keywords: Diacylglycerol, Early life programming, Insulin resistance, Milk fat globule membrane, Mitochondrial function, Supramolecular structure of lipid droplets • Bioblast editor: Plangger M • O2k-Network Lab: DE Duesseldorf Roden M, DE Cologne Pesta D, NL Maastricht Schrauwen P, NL Wageningen Keijer J

On terminology

» Mitochondrial states and rates - terminology beyond MitoEAGLE 2020

For harmonization of terminology on respiratory states and rates, see

• Gnaiger E et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun 2020.1. https://doi.org/10.26124/bec:2020-0001.v1

Labels:

MitoEAGLE terminology 

Labels: MiParea: Respiration, Developmental biology, Exercise physiology;nutrition;life style 

Organism: Mouse  Tissue;cell: Skeletal muscle, Liver  Preparation: Permeabilized tissue 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, NS, ROX  HRR: Oxygraph-2k, O2k-Fluorometer 

2022-08