Microcystin-LR (MC-LR) is a cyanobacterial metabolite produced during cyanobacterial blooms and is toxic to aquatic animals, and the liver is the main targeted organ of MC-LR. To comprehensively understand the toxicity mechanism of chronic exposure to environmental levels of MC-LR on the liver of fish, juvenile Nile tilapia were exposed to 0 μg/L (control), 1 μg/L (M1), 3 μg/L (M3), 10 μg/L (M10), and 30 μg/L (M30) MC-LR for 60 days. Then, the liver hepatotoxicity induced by MC-LR exposure was systematically evaluated via histological and biochemical determinations, and the underlying mechanisms were explored through combining analysis of biochemical parameters, multi-omics (transcriptome and metabolome), and gene expression. The results exhibited that chronic MC-LR exposure caused slight liver minor structural damage and lipid accumulation in the M10 group, while resulting in serious histological damage and lipid accumulation in the M30 group, indicating obvious hepatotoxicity, which was confirmed by increased toxicity indexes (i.e., AST, ALT, and AKP). Transcriptomic and metabolomic analysis revealed that chronic MC-LR exposure induced extensive changes in gene expression and metabolites in six typical pathways, including oxidative stress, apoptosis, autophagy, amino acid metabolism, primary bile acid biosynthesis, and lipid metabolism. Taken together, chronic MC-LR exposure induced oxidative stress, apoptosis, and autophagy, inhibited primary bile acid biosynthesis, and caused fatty deposition in the liver of Nile tilapia.

The replacement of fishmeal with plant protein is widely regarded as a key strategy for sustainable aquaculture. However, carnivorous marine fish often show limited tolerance to fishmeal-free diets. Here, we investigated growth performance, hepatic physiological responses, and molecular mechanisms underlying adaptation to a soy protein concentrate-based diet (SPCD) in golden pompano (Trachinotus ovatus). An 8-week feeding trial was conducted under communal rearing conditions, followed by the phenotypic stratification of SPCD-fed fish into high- and low-growth subgroups. Growth performance, serum biochemical indices, and liver histology were assessed, and integrated transcriptomic and metabolomic analyses were performed on liver tissue. At the population level, the SPCD resulted in reduced growth, a lower feed intake, and decreased feed utilization efficiency compared with a fishmeal-based diet. Notably, marked inter-individual variation was observed: fish fed the SPCD exhibited significantly lower final body weights and a higher FCR compared with the FMD group (p < 0.001), and pronounced growth divergence was observed between the PB and PS subgroups, with a subset of SPCD-fed fish maintaining growth comparable to fishmeal-fed controls, whereas others exhibited severely constrained growth. Divergent phenotypes were associated with distinct hepatic alterations, including aggravated vacuolation, the enrichment of tight junction-related and immune regulatory pathways, and the broad reprogramming of lipid metabolism. Integrated multi-omics analysis identified arachidonic acid metabolism as the most significantly perturbed pathway, characterized by altered membrane phospholipid composition, the upregulation of RARRES3L, increased COX/LOX-derived eicosanoids, and the suppression of the CYP–EET branch. Collectively, these findings indicate that soy protein replacement induces coordinated hepatic structural and metabolic remodeling, with tight junction disruption and arachidonic acid metabolic reprogramming contributing to inflammatory imbalance and divergent growth phenotypes in T. ovatus.

This study investigated the effects of chronic MC-LR exposure (0 μg/L [Control], 1 μg/L [M1], 3 μg/L [M3], 10 μg/L [M10], and 30 μg/L [M30]) on the muscle nutrient composition, meat quality, and muscle proteomic profile of Nile tilapia (Oreochromis niloticus). In the high-dose group (M30), MC-LR exposure compromised the muscle antioxidant status of Nile tilapia, resulting in reduced meat quality, as evidenced by decreased pH value and water-holding capacity, elevated lipid/protein oxidation, and altered texture parameters (shear force and fragmentation index). Proteomic analysis further revealed a downregulation of proteins associated with ribosomes, suggesting an impairment of muscle protein synthesis in the M30 group. Moreover, despite chronic exposure, only low levels of MC-LR accumulated in the muscle tissue, indicating a negligible health risk to consumers. Collectively, these findings offered valuable insights into the impact of environmental MC-LR contamination on fish muscle quality and nutritional value.