| In vertebrates, fish are recognized for their inherent metabolic challenges associated with glucose regulation, often described as congenitally "diabetic." This phenomenon stems from their limited capacity for effective glucose metabolism in response to high-carbohydrate diets, resulting in persistent hyperglycemia that adversely impacts growth performance. Impaired insulin sensitivity and dysfunction in insulin signaling—characterized by compromised insulin receptor function, blocked insulin cascades, and a failure to activate critical signaling pathways, such as the PI3K/AKT pathway—have been identified as key factors contributing to this metabolic disorder. This study aimed to investigate the application of metformin, a biguanide compound with recognized hypoglycemic properties, in ameliorating the adverse effects of high-carbohydrate diets in hybrid grouper (Epinephelus lanceolatus × E. fuscoguttatus)The hybrid grouper has emerged as a significant aquaculture species due to its high market value and growing demand. However, diets rich in carbohydrates pose a challenge for efficient glucose metabolism in this species. Fish typically display a reduced effectiveness in processing glucose following the consumption of carbohydrate-heavy feeds, leading to metabolic disturbances characterized by elevated blood glucose levels, which can negatively influence growth rates, feed conversion efficacy, and overall health. Metformin, chemically known as 1,1-dimethylbiguanide, has demonstrated potential in enhancing insulin receptor functionality, attenuating hepatic gluconeogenesis, and facilitating glucose uptake and storage in various tissues, thereby contributing to glucose homeostasis.In this study, a total of 540 pearl gentian grouper, averaging 10.44±0.01 g, were selected and randomly distributed into six treatment groups, each consisting of three replicates with 30 fish per replicate. We formulated six iso-nitrogenous and iso-lipid diets: one positive control (20% carbohydrate, PC), one negative control (30% carbohydrate, T0), and four experimental groups supplemented with metformin at concentrations of 0.2% (T2), 0.4% (T4), 0.6% (T6), and 0.8% (T8) relative to the negative control. A total of 540 uniformly sized and healthy hybrid grouper, with an average weight of 10.44±0.01 g, were randomly divided into six groups of three replicates each, with 30 fish in each replicate. The fish were then reared for eight weeks. The results of the experiment demonstrated that the levels of carbohydrate and metformin in the feeds had no statistically significant effect (P > 0.05) on the feed coefficient ratio (FCR) and survival rate (SR). The high-carbohydrate feed resulted in a reduction in the weight gain rate (WGR) and specific growth rate (SGR) of hybrid grouper, in comparison to the control group (P>0.05). Mean final body weight (FBW), weight gain rate (WGR) and specific growth (SGR) gradually decreased and showed a linear model as the level of metformin in the feed increased, reaching a minimum in the T8 group, and were significantly lower compared to the PC group (P<0.05). The administration of a high-carbohydrate diet resulted in a notable elevation in the viscerosomatic index (VSI), accompanied by a pronounced reduction in the morphological index of condition factor (CF) (P < 0.05). However, this dietary intervention did not elicit a discernible impact on the hepatosomatic indices (HSI) (P < 0.05). As the level of metformin in the feed increased, the quadratic model was observed for both VSI and HSI, with both reaching a minimum value in the T08 group. However, no significant effect was noted for metformin on CF(P > 0.05). The administration of high-carbohydrate diets resulted in a notable elevation in serum glucose (GLU), triglyceride (TG), and low-density lipoprotein (LDL) levels, accompanied by a pronounced reduction in serum insulin (INS) and high-density lipoprotein (HDL) levels (P < 0.05). However, no discernible impact was observed on TC levels (P > 0.05). As the metformin concentration in the diet increased, serum GLU, TG and LDL levels decreased significantly (P < 0.05), reaching a minimum in the T2, T6 and T8 groups, respectively. All three exhibited a quadratic model. Conversely, serum HDL levels increased significantly (P < 0.05), reaching a maximum in the T8 group and displaying a linear model. Furthermore, the maximum value was reached in the T8 group, which demonstrated a linear model. Additionally, serum HDL content increased significantly (P < 0.05) and reached the maximum value in the T8 group, which also showed a linear model. The serum HDL content increased significantly (P < 0.05), reaching the maximum value in the T8 group and exhibiting a linear model. Conversely, the serum TC content demonstrated a decreasing trend (P > 0.05), reaching the minimum value in the T8 group and exhibiting a linear model. Additionally, the serum insulin content exhibited no significant effect (P > 0.05). High-carbohydrate and metformin levels did not significantly affect the alpha diversity and abundance of the intestinal flora of hybrid grouper (P>0.05). Analyzing the intestinal flora, high-carbohydrate diets increased the relative abundance of Proteobacteria and photobacterium (P > 0.05), and the relative abundance of Firmicutes and brevibacillus in the intestinal increased while that of photobacterium decreased after supplementation of metformin in high-carbohydrate diets. In the context of this study, high-carbohydrate diet inhibited growth performance, decreased insulin sensitivity, and increased the abundance of intestinal pathogenic bacteria in the hybrid grouper. In the context of the present study, the provision of a high-sugar diet augmented with 0.2% metformin resulted in alterations to the composition of intestinal microorganisms, thereby enhancing the disruption of glucose metabolism in the intestinal flora of grouper. This disruption was induced by the high-carbohydrate diet, which promoted glycolysis and inhibited gluconeogenesis, thus regulating glucose homeostasis. This, in turn, facilitated an improvement in the utilisation rate of carbohydrates in pearl gentian grouper. |
