Betancor, M. B. | bioRxiv Science

bioRxiv2026

Spermidine enhances metabolic flexibility and attenuates inflammation associated with ageing in farmed Atlantic salmon

Metabolic ageing and associated changes in lipid mobilisation have been most heavily studied in humans and model taxa, yet remain poorly understood in farmed animals, with potentially important uncharacterised implications for health and welfare outcomes in food production systems. Here, we study both processes in domesticated Atlantic salmon (Salmo salar), the worlds most commercially valuable farmed fish, comparing three stages of aquaculture production. Our sampling captures a key life-cycle change where juvenile fish transition from freshwater into seawater (smoltification), followed by the ongoing ageing process during a final period of growth in seawater. Integrating lipidomics and proteomics of visceral adipose and skeletal muscle tissue, we firstly identified a metabolic-ageing profile akin to that observed in humans, which was distinct from lipid-associated remodelling associated with earlier smoltification. This was marked by impaired triglyceride storage, dysfunctional autophagy-lysosomal pathways, inflammation, fibrosis and reduced pathogen clearance pathways in visceral adipose tissue. In skeletal muscle, ageing was accompanied by reduced metabolic flexibility together with triglyceride and fatty acid accumulation, depletion of phospholipids, and a reduction in free fatty acids required for ATP production. We go on to provide experimental in vivo evidence that dietary spermidine supplementation suppresses adipose inflammation and reverses age-associated metabolic flexibility by re-establishing the buffering role of adipose tissue and enhancing fatty acid metabolism in skeletal muscle. Importantly, spermidine appears to reprogram lipid flux to counter metabolic ageing. As farmed Atlantic salmon exhibit key features of metabolic ageing observed in humans that appear linked to its recent domestication history, this species offers a novel model for ageing related studies of vertebrate metabolism.

molecular biology↗

bioRxiv2024

Rapamycin induced autophagy enhances lipid breakdown and ameliorates lipotoxicity in Atlantic salmon cells.

Autophagy is a highly conserved cellular recycling process essential for homeostasis in all eukaryotic cells. Lipid accumulation and its regulation by autophagy are key areas of research for understanding metabolic disorders in human and model mammals. However, the role of autophagy in lipid regulation remains poorly characterised in non-model fish species of importance to food production, which could be important for managing health and welfare in aquaculture. Addressing this knowledge gap, we investigate the role of autophagy in lipid regulation using a macrophage-like cell line (SHK-1) from Atlantic salmon (Salmo salar L.), the worlds most commercially valuable farmed finfish. Multiple lines of experimental evidence reveal that the autophagic pathway responsible for lipid droplet breakdown is conserved in Atlantic salmon cells. We employed global lipidomics and proteomics analyses on SHK-1 cells subjected to lipid overload, followed by treatment with rapamycin to induce autophagy. This revealed that activating autophagy via rapamycin enhances storage of unsaturated triacylglycerols and suppresses key lipogenic proteins, including fatty acid elongase 6 and acid sphingomyelinase. Moreover, fatty acid elongase 6 was identified as cargo for autophagosomes, suggesting a critical role for autophagy in lipid metabolism in fish. Together, this study establishes a novel model of lipotoxicity and advances understanding of lipid autophagy in fish cells, with significant implications for addressing fish health issues in aquaculture.

cell biology↗