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.