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Due to the wide usage of high-carbohydrate diets in aquaculture, improving the ability of fish to utilize high-carbohydrate diets is one of the important issues in aquaculture. Adipose tissue is an essential organ for storing energy and plays a vital role in glucose homeostasis. In this study, RNA sequencing reveals that docosahexaenoic acid (DHA) promoted the expression of the glucose metabolism related-genes in grass carp adipocytes, raising the hypothesis that DHA may attenuate the adverse effect of high-carbohydrate diets on fish via promoting glucose metabolism in adipose tissue. To verify this hypothesis, a total of 180 juvenile grass carp (14.24 ± 0.43 g) and a total of 180 largemouth bass (40.03 ± 0.12 g) were randomly distributed into 18 tanks (200 L), respectively, and fed with high-carbohydrate diets containing DHA. The results showed that high-carbohydrate diets promoted glycolysis and inhibited lipolysis and fatty acid β-oxidation, leading to the excessive accumulation of abdominal fat and adipose tissue inflammation. After feeding high-carbohydrate diets supplementation with DHA, glucose transporter type 4 (GLUT4) mediated-glucose uptake was increased in adipose tissue, resulting in significantly decreased blood glucose in grass carp and largemouth bass (P < 0.05). And then, the glucose was converted to triglyceride through the glucose-6-phosphate dehydrogenase (G6PD) mediated-pentose phosphate pathway, de novo synthesis of fatty acids and triglyceride (TG) synthesis. Subsequently, the resulting TG was broken down through lipolysis and fatty acid β-oxidation. These reprogrammed metabolic processes inhibited the excessive accumulation of abdominal fat. In addition, DHA attenuated inflammation in adipose tissue, and further reduced the levels of inflammatory cytokines in serum (P < 0.05), indicating that DHA promotes healthy adipose tissue remodeling. Ultimately, these benefits improved the growth performance of grass carp and largemouth bass fed with high-carbohydrate diets. Taken together, our study indicates that adipose tissue is an important target for improving the negative effects of high-carbohydrate diets, and DHA could promote healthy adipose tissue remodeling and improve carbohydrate utilization in fish by reprogramming the glucose and lipid metabolism in adipose tissues.