SIRT1 improves carbohydrate utilization of largemouth bass (Micropterus salmoides) through the Akt1/FoxO1 pathway

NAD-dependent deacetylase sirtuin 1 (SIRT1) plays a crucial role in regulating glucose metabolism, making it a potential therapeutic target for diabetes. However, its specific role in ameliorating carbohydrate utilization in carnivorous fish prone to glucose metabolic disorders remains unclear. In the present study, a typical carnivorous fish, largemouth bass were fed low carbohydrate (LC) or high carbohydrate (HC) diet for 8 weeks, followed by histological staining, transcriptomics, blood glucose and glycogen assays, RT-qPCR, and Western blot analysis. The results of the in vivo study demonstrated the limited carbohydrate utilization of this fish species, and high carbohydrate led to abnormal hepatic glycogen deposition, and insulin resistance with the depression of SIRT1. Primary hepatocytes cultured study and hepatic transcriptome analyses confirmed high carbohydrate-induced insulin resistance in vitro, and the role of SIRT1 in improving carbohydrate utilization has been confirmed which was suggested to be mediated by the insulin signal pathway. Meanwhile, the activation of insulin pathway under high glucose condition improved the glucose metabolism and the inactivation of Akt1 attenuates the role of SIRT1 in improving glucose utilization. Additionally, SIRT1 promoted Akt1 and FoxO1 phosphorylation, thereby inhibiting FoxO1's transcriptional activity on gluconeogenic genes and alleviating glycogen accumulation. These findings highlight the critical role of the SIRT1 pathway in improving carbohydrate utilization via the Akt1/FoxO1 pathway and suggest potential strategies to mitigate insulin resistance in carnivorous fish.