Dietary methionine imbalance alters the transcriptional regulation of genes involved in glucose, lipid and amino acid metabolism in the liver of rainbow trout (Oncorhynchus mykiss)

• Dietary methionine deficiency and excess differently affect hepatic gene expression.
• Methionine acts as a signaling molecule regulating not only growth but also metabolism.
• Finely adjust methionine supplementation to fish requirement is essential to avoid potential metabolic side effects.

Supplementation of fish diets with crystalline methionine is needed to overcome the low methionine content of plant based diet and to ensure good growth performances of the farmed fish. The study aimed to investigate the consequences of methionine imbalance on the expression of genes related to hepatic intermediary metabolism in rainbow trout. For this purpose, juvenile trout were fed during 6 weeks diets containing either deficient, adequate or excess levels of methionine. The results indicate that the methionine deficiency increased the expression of the activating transcription factor 4 (ATF4) target genes asparagine synthetase (ASNS), system A amino acid transporter 2 (SNAT2) and cationic amino acid transporter 1 (CAT1) as a result of the activation of the GCN2/eIF2α pathway. In contrast, dietary methionine supplied in excess produced broader changes on hepatic gene expression by increasing the levels of transcripts related to fatty acid synthesis (fatty acid synthesis, FAS) and oxidation (hydroxyacyl-CoA dehydrogenase, HOAD), gluconeogenesis (glucose-6-phosphatase 2, G6Pase2 and phosphoénolpyruvate carboxykinase, PEPCK) and amino acid catabolism (glutamate dehydrogenase 1 and 2, GDH 1 and 2). Methionine excess also led to a post-prandial down-regulation of G6Pase2 and PEPCK gene expression not occurring in fish fed the methionine deficient or adequate diet. This study shows that a dietary methionine imbalance in juvenile trout strongly affects hepatic gene expression and that the response highly depends on the nature of the imbalance: deficiency or excess.Statement of relevancePrecise amino acid supplementation of fish diet.