Nutrient sensing and metabolic changes after methionine deprivation in primary muscle cells of turbot (Scophthalmus maximus L.)

Abstract

The low methionine content in plant-based diets is a major limiting factor for feed utilization by animals. However, the molecular consequences triggered by methionine deficiency have not been well characterized, especially in fish species, whose metabolism is unique in many aspects and important for aquaculture industry. In the present study, the primary muscle cells of turbot (Scophthalmus maximus L.) were isolated and treated with or without methionine for 12 h in culture. The responses of nutrient sensing pathways, the proteomic profiling of metabolic processes, and the expressions of key metabolic molecules were systematically examined. Methionine deprivation (MD) suppressed target of rapamycin (TOR) signaling, activated AMP-activated protein kinase (AMPK) and amino acid response (AAR) pathways. Reduced cellular protein synthesis and increased protein degradation by MD led to increased intracellular free amino acid levels and degradations. MD also reduced glycolysis and lipogenesis while stimulated lipolysis, thus resulted in decreased intracellular lipid pool. MD significantly enhanced energy expenditure through stimulated tricarboxylic acid (TCA) cycle and oxidative phosphorylation. Collectively, our results identified a comprehensive set of transcriptional, proteomic, and signaling responses generated by MD and provided the molecular insight into the integration of cell homeostasis and metabolic controls in fish species.