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Spotlighting the current state of largemouth bass (Micropterus salmoides) aquaculture, this study exhibited the effects of steroidal saponins (SS) on the liver health of largemouth bass under high‐temperature stress. The study consisted of two experiments: the first trial was designed to evaluate the growth performance of fish fed the experimental diets containing SS 0% and 0.1% (SS0 and SS0.1) for 30 days. And then, the second trial was used to evaluate the health of the livers of these fish under high‐temperature (34°C) stress which lasts for 1 week, and the groups were named as SS0, HSS0, SS0.1, and HSS0.1, respectively. In the first feeding trial, except for the higher feeding rate observed in the SS0.1 group (P < 0.05), no significant difference was observed between the groups SS0 and SS0.1 in survival rate, weight gain rate, specific growth rate, and feed conversion rate, respectively. After 1 week of high‐temperature stress, the specific growth rate and weight gain rate of fish were significantly lowered in the HSS0 and HSS0.1 groups (P < 0.05). In terms of feeding rate, the SS0.1 and HSS0.1 groups were significantly higher than the other two groups (P < 0.05). Under high‐temperature stress, gene expressions of caspase-3, caspase-8, caspase-9, tnf-α, il-8, and hsp70 were significantly downregulated in the liver of largemouth bass in the HSS0.1 group (P < 0.05). The activities of antioxidant enzymes, including catalase, total superoxide dismutase, and glutathione peroxidase in the liver, were significantly increased, while the serum enzyme activities of aspartate aminotransferase and alanine aminotransferase were significantly decreased in the HSS0.1 group (P < 0.05). Compared to the HSS0 group, hepatic vacuolization areas of fish in the HSS0.1 group were improved (P < 0.05). Therefore, the results of the study supported that the 0.1% SS used in largemouth bass diet for 30 days could strengthen the liver and body health and help fish resist heat stress. [ABSTRACT FROM AUTHOR]

Simple Summary: The ingestion of higher-lipid diets by fish could lead to excessive lipid deposition and metabolic disorders in vivo. This experiment analyzed the effects of steroidal saponins on hepatic glucose and lipid metabolism in hybrid grouper fed higher-lipid diets using a multi-omics approach. Data from grouper fed diets with 0% and 0.1% steroidal saponins show that 0.1% steroidal saponins inhibited glycogen synthesis, gluconeogenesis, and the arachidonic acid metabolism pathway and activated glycogenolysis, glycolysis, and the fatty acid β-oxidation pathway. This study provides a deeper insight into the glycolipid metabolic processes in the liver of grouper fed higher crude-lipid diets. An analysis of the extent of the effect of steroidal saponin addition on glucose and lipid metabolism in hybrid grouper liver was performed at the transcriptomic and metabolomic levels. Feeds (52% crude protein, 14% crude lipid) were prepared containing 0% (S0), 0.1% (S0.1), and 0.2% (S0.2) steroidal saponins. After eight weeks of feeding trial, compared to the S0 group, the activities of serum albumin, alanine aminotransferase, and aspartate transaminase were significantly lower and the activities of lysozyme, acid phosphatase, and alkaline phosphatase were significantly higher in the S0.1 group (p < 0.05). The superoxide dismutase, catalase, and glutathione peroxidase activities in the livers of the S0.1 group were significantly higher than those of the S0 group, while the malondialdehyde content was significantly lower than that of the S0 group (p < 0.05). There were forty-two differentially expressed genes and thirty-two differential metabolites associated with glucose and lipid metabolism enriched using KEGG and GO. In the S0 group, the expression of prostaglandin-endoperoxide synthase 1, prostaglandin E synthase 1, and thromboxane-2 synthase mRNA was significantly higher than in the S0.1 group (p < 0.05). The expression levels of genes in the S0 group were significantly higher than those in the S0.1 group (p < 0.05), including for glycogen synthase kinase, glucose-6-phosphatase catalytic subunit 2, fructose-1,6-bisphosphatase, phosphoenolpyruvate carboxykinase, glucose transporter 4, and malate dehydrogenase. The expression of mRNA such as fatty acid synthase, acetyl-CoA carboxylase, and sterol regulatory element-binding protein 1 was significantly lower in the S0.1 group than in the S0 group, while the expression of carnitine acyltransferase 1, acyl-CoA synthetase, and acyl-CoA dehydrogenase genes was significantly higher in the S0 group (p < 0.05). In summary, glycogen synthesis, gluconeogenesis, and the arachidonic acid metabolism pathway were inhibited by 0.1% steroidal saponins, and glycogenolysis, glycolysis, the tricarboxylic acid cycle, and the fatty acid β-oxidation pathway were activated. This study aims to provide a reference for the formulation of grouper feeds with a higher crude-lipid level. [ABSTRACT FROM AUTHOR]