LANEH, School of Life Sciences, East China Normal University, Shanghai, China.
HANOVE Research Center, Wuxi, PR China.
Fish Shellfish Immunol. 2023 Sep;140:108969. doi: 10.1016/j.fsi.2023.108969. Epub 2023 Jul 23.
In omnivorous fish, the pyruvate dehydrogenase kinases (PDKs)-pyruvate dehydrogenase E1α subunit (PDHE1α) axis is essential in the regulation of carbohydrate oxidative catabolism. Among the existing research, the role of the PDKs-PDHE1α axis in carnivorous fish with poor glucose utilization is unclear. In the present study, we determined the effects of PDK inhibition on the liver glycolipid metabolism of largemouth bass (Micropterus salmoides). DCA is a PDK-specific inhibitor that inhibits PDK by binding the allosteric sites. A total of 160 juvenile largemouth bass were randomly divided into two groups, with four replicates of 20 fish each, fed a control diet and a control diet supplemented with dichloroacetate (DCA) for 8 weeks. The present results showed that DCA supplementation significantly decreased the hepatosomatic index, triglycerides in liver and serum, and total liver lipids of largemouth bass compared with the control group. In addition, compared with the control group, DCA treatment significantly down-regulated gene expression associated with lipogenesis. Furthermore, DCA supplementation significantly decreased the mRNA expression of pdk3a and increased PDHE1α activity. In addition, DCA supplementation improved glucose oxidative catabolism and pyruvate oxidative phosphorylation (OXPHOS) in the liver, as evidenced by low pyruvate content in the liver and up-regulated expressions of glycolysis-related and TCA cycle/OXPHOS-related genes. Moreover, DCA consumption decreased hepatic malondialdehyde (MDA) content, enhanced the activities of superoxide dismutase (SOD), and increased transforming growth factor beta (tgf-β), glutathione S-transferase (gst), and superoxide dismutase 1 (sod1) gene expression compared with the control diet. This study demonstrated that inhibition of PDKs by DCA promoted glucose utilization, reduced hepatic lipid deposition, and improved oxidative stress in largemouth bass by increasing pyruvate OXPHOS. Our findings contribute to the understanding of the underlying mechanism of the PDKs-PDHE1α axis in glucose metabolism and improve the utilization of dietary carbohydrates in farmed carnivorous fish.
在杂食性鱼类中，丙酮酸脱氢激酶（PDKs）-丙酮酸脱氢酶 E1α 亚基（PDHE1α）轴在碳水化合物氧化分解代谢的调节中是必不可少的。在现有的研究中，PDKs-PDHE1α 轴在葡萄糖利用能力差的肉食性鱼类中的作用尚不清楚。本研究测定了 PDK 抑制对大口黑鲈（Micropterus salmoides）肝脏糖脂代谢的影响。DCA 是一种 PDK 特异性抑制剂，通过结合别构位点抑制 PDK。总共 160 尾幼龄大口黑鲈随机分为两组，每组 4 个重复，20 尾鱼，分别饲喂对照饲料和对照饲料加二氯乙酸（DCA）8 周。结果表明，与对照组相比，DCA 补充显著降低了大口黑鲈的肝体比、肝脏和血清中的甘油三酯以及总肝脂质。此外，与对照组相比，DCA 处理显著下调了与脂生成相关的基因表达。此外，DCA 补充显著降低了 pdk3a 的 mRNA 表达，增加了 PDHE1α 的活性。此外，DCA 补充提高了肝脏中的葡萄糖氧化分解代谢和丙酮酸氧化磷酸化（OXPHOS），表现为肝脏中丙酮酸含量降低，糖酵解和 TCA 循环/OXPHOS 相关基因表达上调。此外，与对照饲料相比，DCA 消耗降低了肝脏丙二醛（MDA）含量，增强了超氧化物歧化酶（SOD）的活性，并增加了转化生长因子β（tgf-β）、谷胱甘肽 S-转移酶（gst）和超氧化物歧化酶 1（sod1）基因的表达。本研究表明，DCA 抑制 PDKs 通过增加丙酮酸 OXPHOS 促进葡萄糖利用，减少肝脏脂质沉积，改善大口黑鲈的氧化应激。我们的研究结果有助于理解 PDKs-PDHE1α 轴在葡萄糖代谢中的作用机制，并提高养殖肉食性鱼类对饲料碳水化合物的利用。
