Multiomics Reveals a Production Signature Resembling Mammalian Metabolic Ageing and That Dietary Spermidine Enhances Lipid Handling in Farmed Salmon.

Abstract

Metabolic ageing and associated changes in lipid mobilisation have been heavily studied in humans and model taxa, yet remain poorly understood in farmed animals, with potentially important implications for health and welfare outcomes. Here, we compared three stages of aquaculture production in Atlantic salmon (Salmo salar), the world's most commercially valuable farmed fish. Our sampling captures smoltification, a key life-cycle transition, followed by the metabolic changes occurring during growth in seawater. Integrating lipidomics and proteomics of visceral adipose and skeletal muscle tissue, we firstly identify production-associated tissue specific molecular signatures resembling mammalian metabolic ageing, which were distinct from lipid-associated remodelling following smoltification. This was marked by impaired triglyceride storage alongside proteomic changes consistent with dysfunctional autophagy-lysosomal pathways, inflammation, fibrosis and reduced pathogen clearance pathways in visceral adipose tissue. In skeletal muscle, this metabolic-ageing related phenotype was accompanied by downregulation of protein markers of substrate utilisation, reduction in free fatty acids for energy production, triglyceride accumulation, depletion of phospholipids and increased abundance of protein markers associated with senescence. We finally provide in vivo experimental evidence that dietary spermidine supplementation in seawater stage salmon remodels the distribution of fatty acids in both adipose tissue and skeletal muscle. Importantly, this occurred in parallel to changes in lipid and protein markers that may reprogram lipid handling, supporting a hypothesis that spermidine supplementation counters the proposed metabolic ageing related phenotype. As farmed salmon exhibit multiple features of human metabolic ageing linked to its recent domestication, this species offers a novel model for vertebrate ageing studies.

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