Inhibition of pyruvate dehydrogenase kinase increases carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity

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dc.contributor.authorYuan Luo
dc.contributor.authorWen-Hao Zhou
dc.contributor.authorRui-Xin Li
dc.contributor.authorSamwel Mchele Limbu
dc.contributor.authorFang Qiao
dc.contributor.authorLi-Qiao Chen
dc.contributor.authorMei-Ling Zhang
dc.contributor.authorZhen-Yu Du
dc.date.accessioned2022-08-05T17:38:30Z
dc.date.available2022-08-05T17:38:30Z
dc.date.issued2022-06-24
dc.description.abstractPyruvate 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 with control diet without dichloroacetate (DCA0) (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 doseDCA3.75 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.en_US
dc.description.sponsorshipNational Key R & D Program of China (2018YFD0900400)en_US
dc.identifier.citationYuan Luo, Wen-Hao Zhou, Rui-Xin Li, Samwel Mchele Limbu, Fang Qiao, Li-Qiao Chen, Mei-Ling Zhang, and Zhen-Yu Du (2022). Inhibition of pyruvate dehydrogenase kinase increases carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity. Animal Nutrition, https://doi.org/10.1016/j.aninu.2022.06.011en_US
dc.identifier.doihttps://doi.org/10.1016/j.aninu.2022.06.011
dc.identifier.urihttp://hdl.handle.net/20.500.11810/5882
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.subjectDichloroacetateen_US
dc.subjectGlucose utilizationen_US
dc.subjectInsulin sensitivityen_US
dc.subjectNile tilapiaen_US
dc.subjectPDK2/4-PDHE1α axisen_US
dc.titleInhibition of pyruvate dehydrogenase kinase increases carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivityen_US
dc.typeJournal Article, Peer Revieweden_US
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