Abstract
BackgroundEarly nutritional programming affects a series of metabolism, growth and development in mammals. Fish also exhibit the developmental plasticity by early nutritional programming. However, little is known about the effect of early amino acid programming on growth and metabolism.MethodsIn the present study, zebrafish (Danio rerio) was used as the experimental animal to study whether early leucine stimulation can programmatically affect the mechanistic target of rapamycin (mTOR) signaling pathway, growth and metabolism in the later life, and to undercover the mechanism of epigenetic regulation. Zebrafish larvas at 3 days post hatching (dph) were raised with 1.0% leucine from 3 to 13 dph during the critical developmental stage, then back to normal water for 70 days (83 dph).ResultsThe growth performance and crude protein content of zebrafish in the early leucine programming group were increased, and consistent with the activation of the mTOR signaling pathway and the high expression of genes involved in the metabolism of amino acid and glycolipid. Furthermore, we compared the DNA methylation profiles between the control and leucine-stimulated zebrafish, and found that the methylation levels of CG-differentially methylated regions (DMGs) and CHH-DMGs of genes involved in mTOR signaling pathway were different between the two groups. With quantitative PCR analysis, the decreased methylation levels of CG type of Growth factor receptor-bound protein 10 (Grb10), eukaryotic translation initiation factor 4E (eIF4E) and mTOR genes of mTOR signaling pathway in the leucine programming group, might contribute to the enhanced gene expression.ConclusionsThe early leucine programming could improve the protein synthesis and growth, which might be attributed to the methylation of genes in mTOR pathway and the expression of genes involved in protein synthesis and glycolipid metabolism in zebrafish. These results could be beneficial for better understanding of the epigenetic regulatory mechanism of early nutritional programming.
Highlights
The nutritional programming stimulus exerted at the critical stages of early ontogeny might have persistent consequences on physiological functions in later life stages in mammals [1]
We found that 21 CHH-differentially methylated regions (DMGs) involved in mechanistic target of rapamycin (mTOR) signaling pathway, exhibited the higher levels of DNA methylation in fish of the leucine programming group than those of the control group (Fig. 5b)
To highlight the potential role of methylation of key genes in mTOR signaling pathway with early leucine programming, we examined the mRNA expression of four genes in mTOR signaling pathway, including Growth factor receptorbound protein 10 (Grb10), eukaryotic translation initiation factor 4E (eIF4E), mTOR and WD repeat-containing protein 24 (Wdr24)
Summary
The nutritional programming stimulus exerted at the critical stages of early ontogeny might have persistent consequences on physiological functions in later life stages in mammals [1]. Previous studies have been undertaken in fish to determine if the metabolic pathway can be influenced in later life via early nutritional programming [3,4,5,6]. At the critical stage of early development of the individual, fish have significant developmental plasticity by early nutritional programming, as in mammals [7]. Long-chain n-3 high unsaturated fatty acids programming during the critical developmental stage could have a persistent impact on growth performance and lipid metabolism in later life of Siberian sturgeon (Acipenser baerii Brandt) [8]. Little is known about the effects of early amino acid programming on growth and nutritional metabolism. Nutritional programming affects a series of metabolism, growth and development in mammals. Little is known about the effect of early amino acid programming on growth and metabolism
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