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Remodelling of the hepatic epigenetic landscape of glucose-intolerant rainbow trout by nutritional status and dietary carbohydrates
In the context of the replacement of fishmeal and fish oil by alternative ingredients in aquafeeds, a better knowledge of the regulation of intermediary metabolism in trout is needed. Analyzing the modulation of the hepatic epigenetic landscape in rainbow trout genome by nutritional status and nutrients shed new light on processes which contribute to the poor utilization of some of this new ingredients such as dietary carbohydrates.
Context and challenge :
In order to improve the sustainability of the aquaculture production of salmonids, it is now essential to develop alternative aquafeeds without fishmeal and fish oil as ingredients. However, numerous metabolic locks still exist in salmonids preventing to increase the part of new ingredients such as dietary carbohydrates. Trout metabolism has been thoroughly investigated at physiological, biochemical and transcriptional levels since the 90’s to try to explain the mechanisms underlying these locks. However, there is little information concerning epigenetic modifications mediated by nutritional status or nutrients and their physiological consequence in rainbow trout. Changes in the epigenome are nevertheless partly in response to environmental factors, including nutrition, which will subsequently lead to adjustment of metabolism. Epigenetic modifications are thus known as possible mechanisms through which nutritional status could initiate a metabolic memory by changing the chromatin structure and consequently the regulation of the genes, and hence their transcription . These mechanisms have been also reported to be affected in metabolic diseases linked to disturbance of glucose metabolism such as diabetes or hyperglycaemia.Therefore, exploring the epigenome might provide new elements to enhance our understanding of intermediary metabolism and nutritional phenotypes in trout fed diets containing new ingredients.
Rainbow trout belongs to a high trophic level. It thus exhibits a poor utilization of dietary carbohydrates characterized by reduced growth and prolonged postprandial hyperglycemia when fed a high carbohydrate diet.In the present study we first assessed in trout whether and how nutritional status (i.e, fasted vs fed fish with or without dietary carbohydrates) affected global epigenome modifications by targeting DNA methylation and histone marks previously reported to be affected in metabolic diseases linked to disturbance of glucose metabolism (permissive H3K4me3, H3K9ac and H3K36me3, and repressive H3K9me3). As changes in the global epigenome induced by environmental modifications may have a potential epigenetic impact at the gene regulation level, we then examined whether dietary carbohydrates could affect the epigenetic landscape at duplicated gluconeogenic gene loci previously reported to display mRNA level changes in trout fed a high carbohydrate diet. We specifically highlighted global hypomethylation of DNA and hypoacetylation of H3K9 in trout fed a HighCHO diet, a well-described phenotype in diabetes.g6pcb2 ohnologs (glucose-6-phosphatase encoding genes) were also hypomethylated at specific CpG sites in these animals according to their up-regulation. Our findings demonstrated that the hepatic epigenetic landscape can be affected by both nutritional status and dietary carbohydrates in trout.
The mechanism underlying the setting up of these epigenetic modifications has now to be explored in order to improve understanding of its impact on the glucose intolerant phenotype in carnivorous teleosts. Also, functional analysis will be conducted to establish the extent to which DNA methylation could be a mechanism involved in the atypical up-regulation ofg6pcgenes, genes supposed to be involved in the glucose-intolerant phenotype in trout.
Marandel, L. et al. Remodelling of the hepatic epigenetic landscape of glucose-intolerant rainbow trout (Oncorhynchus mykiss) by nutritional status and dietary carbohydrates. Scientific Reports 6, 32187, doi:10.1038/srep32187
Marandel, L., Seiliez, I., Veron, V., Skiba-Cassy, S. and Panserat, S. (2015). New insights into the nutritional regulation of gluconeogenesis in carnivorous rainbow trout (Oncorhynchus mykiss): a gene duplication trail. Physiol Genomics 47, 253-63.