The beneficial effects of metformin inclusion on growth performance, glucose utilization, antioxidant capacity and apoptosis of largemouth bass (Micropterus salmoides) fed with high dietary carbohydrates

Abstract

The diabetic feature limits the utilization of dietary carbohydrates in carnivorous fish, and excessive dietary carbohydrate usually cause negative effects on health and growth of these fish. In this study, a 9-weeks' feeding experiment was conducted to figure out the influence of dietary metformin (MET), an effective agent for diabetes in mammals, supplementation on largemouth bass, a typical carnivorous fish, feeding high dietary carbohydrates. Compared with the low dietary carbohydrates (LC) group, high dietary carbohydrates (HC) impaired growth performance, which was improved by the inclusion of MET in HC diets. Meanwhile, compared with the HC group, dietary MET supplementation significantly reduced hepatic glycogen and serum glucose contents. Additionally, on the transcriptional level, HC repressed the insulin pathway and induced imbalanced regulation of glycolysis and glycogenesis compared with LC group. However, the MET supplementation significantly enhanced the genes' expression involved in insulin pathway (ira, irb, irs1, pi3kr1, akt1) followed by the activated expression of glycolysis (adpgk, pfkl, and pk) and inhibited expression of glycogenesis (g6pc and pepck). HC significantly reduced antioxidant capacity compared with the LC group, which was reversed with MET supplementation at both transcriptional and enzymatic levels. Additionally, high dietary carbohydrates inhibited apoptosis, which was activated with the inclusion of MET with the inhibition of bcl2/bax ratio and the activation of apoptosis-promoting genes (nfac1-l, arel1, and aif2). In summary, dietary MET inclusion in high carbohydrate diet improved glucose utilization via activating the insulin pathway, and further enhance the growth performance and antioxidant capacity.