Abstract
The rainbow trout, a carnivorous fish, displays a ‘glucose-intolerant’ phenotype revealed by persistent hyperglycaemia when fed a high carbohydrate diet (HighCHO). Epigenetics refers to heritable changes in gene activity and is closely related to environmental changes and thus to metabolism adjustments governed by nutrition. In this study we first assessed in the trout liver whether and how nutritional status affects global epigenome modifications by targeting DNA methylation and histone marks previously reported to be affected in metabolic diseases. We then examined whether dietary carbohydrates could affect the epigenetic landscape of duplicated gluconeogenic genes previously reported to display changes in mRNA levels 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 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.
Highlights
Was hypothesized to be involved in the establishment of the glucose-intolerant phenotype in trout fed a high carbohydrate diet
In the present study we first assessed in trout whether and how nutritional status 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
As changes in the global epigenome induced by environmental modifications may have a potential epigenetic impact at the gene regulation level, we 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
Summary
Was hypothesized to be involved in the establishment of the glucose-intolerant phenotype in trout fed a high carbohydrate diet. As changes in the global epigenome induced by environmental modifications may have a potential epigenetic impact at the gene regulation level, we 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 (i.e, pck[1], fbp1b1, fbp1b2, g6pca, g6pcb1a, g6pcb1b, g6pcb2a, g6pcb2b9, and not fbp1a and pck[2] the mRNA levels of which remained stable). This last step would provide new information to improve understanding of how duplicated genes encoding the same enzyme, but which are regulated differently by dietary carbohydrates, are regulated
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