Micronutrient supplementation affects transcriptional and epigenetic regulation of lipid metabolism in a dose-dependent manner

Abstract

Micronutrients (vitamins and minerals) have been less well studied compared to macronutrients (fats, proteins, and carbohydrates) although they play important roles in growth, metabolism, and maintenance of tissues. Hence, there is growing interest to understand the influence of micronutrients across various aspects in nutritional research. In the last two decades, aquaculture feeds have been shifted to containing more plant-based materials to meet the increasing demand and maintain the sustainability in the industry. A recent whole life cycle feeding trial of Atlantic salmon ( Salmo salar ) with graded levels of micronutrient packages has concluded that the levels of several B-vitamins and microminerals need to be increased from the current recommendation levels for optimal growth and fish welfare when plant-based diets are used. Here, we show the effect of micronutrient supplementation on hepatic transcriptional and epigenetic regulation in a dose dependent manner. . Specifically, our aim is to reveal the mechanisms of altered cell metabolism, which results in improved growth performance by micronutrient surpluses, at gene expression and DNA methylation levels. Our results strongly indicate that micronutrient supplementation suppresses gene expression in lipid metabolism in a dose-dependent manner and broadly affects DNA methylation in cell-adhesion and cell-signalling. In particular, it increases DNA methylation levels on the acetyl-CoA carboxylase alpha promoter in a concentration-dependent manner, which further suggests that acetyl-CoA carboxylase alpha is an upstream epigenetic regulator controlling its downstream lipid biosynthesis activities. This study demonstrates a comprehensive analysis to reveal an important role of micronutrients in lipid metabolism through epigenetic control of gene expression.

Micronutrient supplementation affects DNA methylation in male gonads with potential intergenerational epigenetic inheritance involving the embryonic development through glutamate receptor-associated genes

“…As summarised in previous studies [ 11 , 12 ], both medium (L2) and high (L3) doses of micronutrients contributed to improved growth performance when compared to the control diet (L1) by body weight, hepatosomatic index (HSI) [ 25 ], and Fulton's condition factor (K) [ 26 ]. At the smolt stage, L2 showed the best growth followed by L3 in terms of weight gain, whereas at harvest, both L2 and L3 showed significantly better growth (Fig.…”

“…DNA methylation is a reversible and heritable covalent modification of DNA found in the genomes of plants and animals [ 8 – 10 ]. Cytosine methylation at CpG sites is the most common form of DNA methylation in vertebrates [ 8 ] including Atlantic salmon ( Salmo salar ) [ 11 ].…”

“…The NP contained 24 micronutrient components, including 13 vitamins, eight minerals, two crystalline amino acids, and cholesterol (Table 1 ). Previous studies that analysed fish from the same feeding trial reported that micronutrient supplementation enhanced growth performance [ 12 ] and epigenetically improved lipid metabolism in liver [ 11 ]. Nevertheless, the intergenerational impact of DNA methylation on offspring remained unanswered.…”

Summer Is Coming! Tackling Ocean Warming in Atlantic Salmon Cage Farming

“…It may also be worth investigating how variable levels of micronutrients (e.g., vitamins and minerals) in formulated aquafeeds can promote epigenetic regulation in a dose-dependent manner. While the sole available study to date on this topic specifically monitored gene expression in the lipid metabolism of Atlantic salmon parr and smolts [ 137 ], it will be certainly worth exploring if epigenetic regulation of biomarker genes associated with thermal tolerance may also be achieved by adjusting micronutrients incorporation in aquafeeds. Ultimately, the development of these approaches within a context of climate change mitigation is paramount to foster aquaculture production over the next decades.…”

Using nutrigenomics to evaluate microdiet performance in pike silverside larvae

“…Even though the effects in whole gene expression profiles of live feed versus microdiet for fish larvae are unknown, recent studies have enriched microdiets with specific molecules to assess the performance and development while focussing on the expression of a few target genes involved in specific pathways at early larvae stages (Alves-Martins et al, 2011;Canada et al, 2016;Izquierdo et al, 2019;Khoa et al, 2020;Saito et al, 2020;Terova et al, 2018). In this context, a nutrigenomic approach may provide a broader view of the transcriptional changes induced by a diet which ultimately may have an impact on fish development and provide important information for future diets following fish requirements (García de la Serrana et al, 2012;Martin & Król, 2017;Ulloa et al, 2011).…”