Back to search

HAVBRUK2-Stort program for havbruksforskning

Nutrient-responsive epigenetic programming in Atlantic salmon and zebrafish muscle growth

Alternative title: Næringsstoffbasert epigenetisk programmering av muskelvekst i Atlantisk laks og sebrafisk

Awarded: NOK 2.2 mill.

The aquaculture industry has been replacing fishmeal as the main feed ingredient with plant-based alternatives due to both economic considerations and increased demand in general. Novel feeds in Atlantic salmon farming contain higher levels of plant-based compared to marine ingredients that change the micronutrient composition of B-vitamins and indispensable amino acids affecting the growth of farmed fish. A moderate surplus of the 1C-nutrients methionine, folic acid, vitamin B6 and B12 above current recommendations for Atlantic salmon improved growth and reduced relative liver size, which is positive for the state of health. This project aimed to understand how moderate surplus of the 1C-nutrients in the diet to Atlantic salmon affect nutrient retention, nutrient composition in muscle, growth and health throughout smoltification. The project explored the interaction between nutrients and gene expression through epigenetic gene regulation that programs muscle cells in response to micronutrient levels in the feed. Epigenetics includes several different mechanisms such as histone tail modifications and DNA methylation that together regulate mRNA expression and thereby control metabolism, which is one underlying explanation for nutritional programming. We profiled metabolites, active signaling pathways and gene expression in salmon muscle tissue and results revealed an increased capacity for using amino acids to form new proteins when salmon was fed more 1C-nutrients in the diet. At the same time, antioxidant capacity was also improved through smoltification with more 1C-nutrients in the diet. The control group, on the other hand, had a lower body weight, showed signs of compensatory growth regulation in muscle and increased fat in the liver after transfer to seawater. Overall, 1C-nutrient dependent effects were significant already at pre-smolt, but differences intensified when analyzing post-smolt muscle. These findings point to the 1C-nutrients that fine-tune the interaction between nutrients and gene expression, which is essential for increased growth capacity through an improved amino acid utilization for protein synthesis when salmon was fed a moderate surplus of 1C-nutrients throughout smoltification. This work has been published in British Journal of Nutrition. To investigate underlying mechanisms that determine the activity of the signaling pathways and the activity of genes, we have proceeded with epigenetic analyses such as DNA methylation and histone tail modifications in the same fish on which gene expression was measured. Our results highlight potential nutritional programming strategies on post-smolt growth through 1C-nutrient supplementation before and throughout smoltification. Epigenetic changes in early life stages, or as early impact in pre-smolts, can program life-long consequences on physiology, robustness and growth in the on-growing post-smolt saltwater period. Epigenetics does not change the genetic material (DNA) itself, but how the genetic material is used. Understanding how growth is controlled by epigenetic mechanisms becomes important for a rapidly growing aquaculture industry whose concerns are to optimize production, sustainability and quality. The knowledge obtained in this project has the potential to customize fish feed composition to maintain healthy fish, and to contribute to further develop innovative methods for nutritional programming to improve fish health and growth.

Our findings highlight potential nutritional programming strategies on how a moderate surplus of the 1C-nutrients methionine, folate, vitamin B6 and B12 prior to biological transformations such as smoltification in salmonids improves growth capacity in post-smolts after seawater transfer. Epigenetic changes in pre-smolts can program life-long consequences on physiology, robustness and growth. Understanding how growth is controlled by fine-tuned nutrient-gene-interactions becomes important for a rapidly growing aquaculture industry in terms of sustainability, quality and optimized production. The knowledge obtained in this project serves as a base for further development of innovative methods for nutritional programming strategies to improve fish health and growth over generations. Results will be made publicly available for re-use and provide valuable documentation important to aquaculture industry for customization of future feeds to produce a robust fish.

The aquaculture industry has been replacing fishmeal as the main feed ingredient with plant-based alternatives due to both economic considerations and increased demand in general. Changes in feed ingredients changes the micronutrient composition of B-vitamins and indispensable amino acids affecting the growth of farmed fish. This project uses both Atlantic salmon to determine how changes in 1-C nutrients (methionine, folate, vitamin B12 and B6) affect muscle growth by studying epigenetic mechanisms (DNA methylation and histone modifications) in Atlantic salmon muscle. Previously, we found loci specific changes in DNA methylation particularly in muscle associated with parental diet. Here, we want to understand how diet affects nutrient retention, muscle composition, growth and health through changing nutrient-responsive epigenetic mechanisms. Histone modifications together with DNA methylation regulate mRNA expression, and thereby control metabolism, which is one underlying mechanistic explanation for nutritional programming. In cooperation with NutrEpi (NRC 267787), we will determine how metabolic, mRNA and DNA methylation profiles in fast muscle change due to plant-based diets with either low or high 1-C nutrient levels throughout smoltification. The project will gain new knowledge on how diet affects nutrient-responsive epigenetic patterns in muscle of Atlantic salmon already at early and sensitive life stages. Epigenetic changes in early life stages, or as early impact in pre-smolts, can program life-long consequences on physiology, robustness and growth. The outcome and impact of this project have potential to customize feed composition in broodstock management to maintain good filet quality and robust fish through nutrition across generations.

Funding scheme:

HAVBRUK2-Stort program for havbruksforskning