Maternal n-3 PUFA supplementation promotes fetal brown adipose tissue development through epigenetic modifications in C57BL/6 mice |
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Authors: | Rong Fan Ashley Mulcahy Toney Yura Jang Seung-Hyun Ro Soonkyu Chung |
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Institution: | 1. Department of Nutrition and Health Sciences, University of Nebraska, Lincoln, NE 68583, USA;2. Department of Biochemistry, University of Nebraska, Lincoln, NE 68583, USA |
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Abstract: | Brown adipose tissue (BAT) is a crucial regulator of energy expenditure. Emerging evidence suggests that n-3 PUFA potentiate brown adipogenesis in vitro. Since the pregnancy and lactation is a critical time for brown fat formation, we hypothesized that maternal supplementation of n-3 PUFA promotes BAT development in offspring. Female C57BL/6 mice were fed a diet containing n-3 PUFA (3%) derived from fish oil (FO), or an isocaloric diet devoid of n-3 PUFA (Cont) during pregnancy and lactation. Maternal n-3 PUFA intake was delivered to the BAT of neonates significantly reducing the n-6/n-3 ratio. The maternal n-3 PUFA exposure was linked with upregulated brown-specific gene and protein profiles and the functional cluster of brown-specific miRNAs. In addition, maternal n-3 PUFA induced histone modifications in the BAT evidenced by 1) increased epigenetic signature of brown adipogenesis, i.e., H3K27Ac and H3K9me2, 2) modified chromatin-remodeling enzymes, and 3) enriched the H3K27Ac in the promoter region of Ucp1. The offspring received maternal n-3 PUFA nutrition exhibited a significant increase in whole-body energy expenditure and better maintenance of core body temperature against acute cold treatment. Collectively, our results suggest that maternal n-3 PUFA supplementation potentiates fetal BAT development via the synergistic action of miRNA production and histone modifications, which may confer long-lasting metabolic benefits to offspring. |
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Keywords: | ARA (arachidonic acid) Cidea (cell death-inducing DNA fragmentation factor α-like effector A) DHA (docosahexaenoic acids) EHMT1 (euchromatic histone N-lysine methyltransferase 1) EPA (eicosapentaenoic acids) eWAT (epididymal white adipose tissue) FO (fish oil) GPR120 (G-protein-coupled receptor 120) HF (high fat) iBAT (interscapular brown adipose tissue) iWAT (inguinal white adipose tissue) Jmjd1 (JmjC domain-containing protein 1) Jmjd3 (JmjC domain-containing protein 3) miRNAs (microRNAs) Prdm16 (PR domain containing 16) n-3 PUFA (omega-3 polyunsaturated fatty acids) (peroxisome proliferator-activated receptor gamma coactivator 1-alpha) PTM (post-translational modifications) sWAT (subcutaneous white adipose tissue) UCP1 (uncoupling protein 1) BAT N-3 PUFA Fish oil Thermogenesis Maternal nutrition |
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