Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity
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 inh...
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KeAi Communications Co., Ltd.
2022-12-01
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| Series: | Animal Nutrition |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405654522000798 |
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| author | Yuan Luo Wenhao Zhou Ruixin Li Samwel M. Limbu Fang Qiao Liqiao Chen Meiling Zhang Zhen-Yu Du |
| author_facet | Yuan Luo Wenhao Zhou Ruixin Li Samwel M. Limbu Fang Qiao Liqiao Chen Meiling Zhang Zhen-Yu Du |
| author_sort | Yuan Luo |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T04:31:02Z |
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| id | doaj.art-06b56984549649fabe35920dc908f225 |
| institution | Directory Open Access Journal |
| issn | 2405-6545 |
| language | English |
| last_indexed | 2024-04-11T04:31:02Z |
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| spelling | doaj.art-06b56984549649fabe35920dc908f2252022-12-29T04:13:23ZengKeAi Communications Co., Ltd.Animal Nutrition2405-65452022-12-01112537Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivityYuan Luo0Wenhao Zhou1Ruixin Li2Samwel M. Limbu3Fang Qiao4Liqiao Chen5Meiling Zhang6Zhen-Yu Du7LANEH, School of Life Sciences, East China Normal University, Shanghai 200241, ChinaLANEH, School of Life Sciences, East China Normal University, Shanghai 200241, ChinaLANEH, School of Life Sciences, East China Normal University, Shanghai 200241, ChinaUniversity of Dar Es Salaam, Department of Aquaculture Technology, Dar Es Salaam 60091, Tanzania; UDSM-ECNU Joint Research Center for Aquaculture and Fish Biology (JRCAFB), Dar Es Salaam 60091, TanzaniaLANEH, School of Life Sciences, East China Normal University, Shanghai 200241, ChinaLANEH, School of Life Sciences, East China Normal University, Shanghai 200241, ChinaLANEH, School of Life Sciences, East China Normal University, Shanghai 200241, ChinaLANEH, School of Life Sciences, East China Normal University, Shanghai 200241, China; ECNU-UDSM Joint Research Center for Aquaculture and Fish Biology (JRCAFB), Shanghai 200241, China; Corresponding author.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.http://www.sciencedirect.com/science/article/pii/S2405654522000798DichloroacetateGlucose utilizationInsulin sensitivityNile tilapiaPDK2/4-PDHE1α axis |
| spellingShingle | Yuan Luo Wenhao Zhou Ruixin Li Samwel M. Limbu Fang Qiao Liqiao Chen Meiling Zhang Zhen-Yu Du Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity Animal Nutrition Dichloroacetate Glucose utilization Insulin sensitivity Nile tilapia PDK2/4-PDHE1α axis |
| title | Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity |
| title_full | Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity |
| title_fullStr | Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity |
| title_full_unstemmed | Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity |
| title_short | Inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in Nile tilapia by regulating PDK2/4-PDHE1α axis and insulin sensitivity |
| title_sort | inhibition of pyruvate dehydrogenase kinase improves carbohydrate utilization in nile tilapia by regulating pdk2 4 pdhe1α axis and insulin sensitivity |
| topic | Dichloroacetate Glucose utilization Insulin sensitivity Nile tilapia PDK2/4-PDHE1α axis |
| url | http://www.sciencedirect.com/science/article/pii/S2405654522000798 |
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