show Abstracthide AbstractPrevious studies have indicated that food intake decreased after feeding a carbohydrate-rich diet in carnivorous fish. However, the molecular mechanism underlying the anorexia caused by high-carbohydrate diets has remained elusive. To identify the molecular mechanism, we domesticated the mandarin fish to feed on carbohydrate-rich diets (8%), and observed the anorexia in mandarin fish of Group B. In mandarin fish of Group B, plasma glucose was significantly higher, hepatic glycogen and plasma triglyceride was significantly lower. Using transcriptome sequencing, mandarin fish of Group B have the activation of mTOR and Jak/STAT pathway, resulting in high level of pepck mRNA and CART neuron. Furthermore, histone methylase SETD1B up-regulated histone H3 tri-methylated at lysine 4 (H3K4me3) to increase pepck mRNA expression, then lead to hyperglycemia. this study initially demonstrates a link between epigenetic mechanism and food intake, it represents a novel molecular mechanism underlying appetite regulation in mandarin fish after feeding a carbohydrate-rich diet.