Pyruvate dehydrogenase kinases (PDKs)-pyruvate dehydrogenase E1α subunit (PDHE1α) axis plays an important role in regulating glucose metabolism in mammals. However, the regulatory function of PDKs-PDHE1α axis in the glucose metabolism of fish is not well known. This study determined whether PDKs inhibition could enhance PDHE1α activity, and improve glucose catabolism in fish. Nile tilapia fingerlings (1.90 ± 0.11 g) were randomly divided into 4 treatments in triplicate (30 fish each) and fed control diet without dichloroacetate (DCA) (38% protein, 7% lipid and 45% corn starch) and the control diet supplemented with DCA, which inhibits PDKs through binding the allosteric sites, at 3.75 (DCA3.75), 7.50 (DCA7.50) and 11.25 g/kg (DCA11.25), for 6 wk. The results showed that DCA3.75, DCA7.50 and DCA11.25 significantly increased weight gain, carcass ratio and protein efficiency ratio (P < 0.05) and reduced feed efficiency (P < 0.05) of Nile tilapia. To investigate the effects of DCA on growth performance of Nile tilapia, we selected the lowest dose DCA3.75 for subsequent analysis. Nile tilapia fed on DCA3.75 significantly reduced the mesenteric fat index, serum and liver triglyceride concentration and total lipid content in whole fish, and down-regulated the expressions of genes related to lipogenesis (P < 0.05) compared to the control. The DCA3.75 treatment significantly improved glucose oxidative catabolism and glycogen synthesis in the liver, but significantly reduced the conversion of glucose to lipid (P < 0.05). Furthermore, the DCA3.75 treatment significantly decreased the PDK2/4 gene and protein expressions (P < 0.05), accordingly stimulated PDHE1α activity by decreasing the phosphorylated PDHE1α protein level. In addition, DCA3.75 treatment significantly increased the phosphorylated levels of key proteins involved in insulin signaling pathway and glycogen synthase kinase 3β (P < 0.05). Taken together, the present study demonstrates that PDK2/4 inhibition by using DCA promotes glucose utilization in Nile tilapia by activating PDHE1α and improving insulin sensitivity. Our study helps to understand the regulatory mechanism of glucose metabolism for improving dietary carbohydrate utilization in farmed fish.

丙酮酸脱氢酶激酶（PDKs）-丙酮酸脱氢酶E1α亚基（PDHE1α）轴在调节哺乳动物葡萄糖代谢中起重要作用。然而，PDKs-PDHE1α轴在鱼类葡萄糖代谢中的调节作用尚不清楚。本研究确定了 PDKs 抑制是否可以增强 PDHE1α 活性，并改善鱼类的葡萄糖分解代谢。尼罗罗非鱼鱼种 (1.90 ± 0.11 g) 随机分为 4 个处理，一式三份（每组 30 条鱼），喂食不含二氯乙酸盐 (DCA) 的对照日粮（38% 蛋白质、7% 脂质和 45% 玉米淀粉），对照日粮补充DCA 通过结合变构位点抑制 PDK，剂量分别为 3.75 (DCA3.75)、7.50 (DCA7.50) 和 11.25 g/kg (DCA11.25)，持续 6 周。结果表明，DCA3.75、DCA7.50 和 DCA11.25 显着增加了体重增加，P  < 0.05) 和降低尼罗罗非鱼的饲料效率 ( P  < 0.05)。为了研究 DCA 对尼罗罗非鱼生长性能的影响，我们选择了最低剂量的 DCA3.75 进行后续分析。与对照相比，饲喂DCA3.75的尼罗罗非鱼显着降低了全鱼的肠系膜脂肪指数、血清和肝脏甘油三酯浓度和总脂质含量，并下调了脂肪生成相关基因的表达（P  < 0.05）。DCA3.75处理显着改善了肝脏中的葡萄糖氧化分解代谢和糖原合成，但显着降低了葡萄糖向脂质的转化（P  < 0.05）。此外，DCA3.75 处理显着降低了 PDK2/4 基因和蛋白质的表达（P  < 0.05)，因此通过降低磷酸化 PDHE1α 蛋白水平来刺激 PDHE1α 活性。此外，DCA3.75处理显着增加了胰岛素信号通路相关关键蛋白和糖原合酶激酶3β的磷酸化水平（P  < 0.05）。总之，本研究表明，使用 DCA 抑制 PDK2/4 通过激活 PDHE1α 和提高胰岛素敏感性来促进尼罗罗非鱼的葡萄糖利用。我们的研究有助于了解葡萄糖代谢的调节机制，以提高养殖鱼类的膳食碳水化合物利用率。