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Neonatal intake of Omega-3 fatty acids enhances lipid oxidation in adipocyte precursors.

ABSTRACT: Establishing metabolic programming begins during fetal and postnatal development, and early-life lipid exposures play a critical role during neonatal adipogenesis. We define how neonatal consumption of a low omega-6 to -3 fatty acid ratio (n6/n3 FA ratio) establishes FA oxidation in adipocyte precursor cells (APCs) before they become adipocytes. In vivo, APCs isolated from mouse pups exposed to the low n6/n3 FA ratio had superior FA oxidation capacity, elevated beige adipocyte mRNAs Ppargc1α, Ucp2, and Runx1, and increased nuclear receptor NR2F2 protein. In vitro, APC treatment with NR2F2 ligand-induced beige adipocyte mRNAs and increased mitochondrial potential but not mass. Single-cell RNA-sequencing analysis revealed low n6/n3 FA ratio yielded more mitochondrial-high APCs and linked APC NR2F2 levels with beige adipocyte signatures and FA oxidation. Establishing beige adipogenesis is of clinical relevance, because fat depots with energetically active, smaller, and more numerous adipocytes improve metabolism and delay metabolic dysfunction.

SUBMITTER: Varshney R

PROVIDER: S-EPMC9800552 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Neonatal intake of Omega-3 fatty acids enhances lipid oxidation in adipocyte precursors.

Varshney Rohan R Das Snehasis S Trahan G Devon GD Farriester Jacob W JW Mullen Gregory P GP Kyere-Davies Gertrude G Presby David M DM Houck Julie A JA Webb Patricia G PG Dzieciatkowska Monika M Jones Kenneth L KL Rodeheffer Matthew S MS Friedman Jacob E JE MacLean Paul S PS Rudolph Michael C MC

iScience 20221206 1

Establishing metabolic programming begins during fetal and postnatal development, and early-life lipid exposures play a critical role during neonatal adipogenesis. We define how neonatal consumption of a low omega-6 to -3 fatty acid ratio (n6/n3 FA ratio) establishes FA oxidation in adipocyte precursor cells (APCs) before they become adipocytes. <i>In vivo</i>, APCs isolated from mouse pups exposed to the low n6/n3 FA ratio had superior FA oxidation capacity, elevated beige adipocyte mRNAs Pparg ...[more]

PMID: 36590177

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Project description:Introduction: Retinopathy of prematurity (ROP) with early vessel loss (Phase I) followed by uncontrolled vessel growth (Phase II) causes visual impairment in premature infants. Although supplementation with n-3 docosahexaenoic acid (DHA) alone has mixed results to prevent ROP, combined supplementation with DHA and n-6 arachidonic acid (ARA) in early postnatal life reduces severe ROP by 50% (Mega Donna Mega study). The underlying mechanisms are unknown. Objectives: To evaluate protective effects and mechanism of combined dietary n-3 DHA and n-6 ARA in a neonatal mouse model of Phase I ROP. Methods: In the Mega Donna Mega study, most preterm infants had early postnatal hyperglycemia episodes, a strong risk factor for severe ROP. We used a neonatal mouse model of hyperglycemia-induced suppression of retinal vascular development (Phase I ROP). Dams were fed diets enriched with 3%DHA or 1%DHA+2%ARA. In P10 milk-fed pups, we assessed retinal vascularization, and proteome, and fatty acid profiles in retina, retinal pigment epithelium (RPE) complex and plasma. In vivo, oligomycin A, a mitochondrial ATP synthase inhibitor, was used to assess mitochondrial participation in the combined lipid protective effects. Results: In 201 (97.6%) of 206 randomized infants there was at least one elevated glucose measurement during the first 14 days. In a neonatal mouse model of hyperglycemia-induced suppression of vascular development, maternal DHA+ARA vs. DHA diet promoted pup retinal vessel growth. Fatty acid profiling confirmed lipid changes in pup plasma and RPE complex in accord with DHA and ARA levels in the maternal diets. Proteomic retinal analysis revealed increased abundance of proteins related to mitochondrial respiration and glucose metabolism in the combined diet. Inhibition of mitochondrial ATP synthase negated the protective effects of the combined diet on retinal vascularization. Conclusion: Combined DHA+ARA oral supplementation in the early postnatal period protects against Phase I ROP in mouse neonates, through enhanced retinal metabolism suggesting the potential of balanced lipid supplementation for preventing ROP.

Dataset Information

Neonatal intake of Omega-3 fatty acids enhances lipid oxidation in adipocyte precursors.

Publications

Neonatal intake of Omega-3 fatty acids enhances lipid oxidation in adipocyte precursors.

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