PDK inhibition promotes glucose utilization and reduces hepatic lipid deposition, and improves oxidative stress in largemouth bass (Micropterus salmoides) by increasing pyruvate oxidative phosphorylation.
PDK inhibition promotes glucose utilization and reduces hepatic lipid deposition, and improves oxidative stress in largemouth bass (Micropterus salmoides) by increasing pyruvate oxidative phosphorylation.
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DOI：
10.1016/j.fsi.2023.108969
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发表时间：
2023-07
影响因子：
4.7
通讯作者：
An-Hui Jin;Yi‐Fan Qian;Jiong Ren;Jin-Gang Wang;Fang Qiao;Meiling Zhang;Z. Du;Yuan Luo
中科院分区：
文献类型：
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作者：
An-Hui Jin;Yi‐Fan Qian;Jiong Ren;Jin-Gang Wang;Fang Qiao;Meiling Zhang;Z. Du;Yuan Luo
在杂食性鱼类中，丙酮酸脱氢酶激酶（PDKs）-丙酮酸脱氢酶E1α亚基（PDHE 1 α）轴在碳水化合物氧化催化的调节中起着重要作用。在现有的研究中，PDKs-PDHE 1 α轴在葡萄糖利用率低的肉食性鱼类中的作用尚不清楚。在本研究中，我们确定了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，通过结合变构位点抑制PDK。将160尾大口黑鲈幼鱼随机分为两组，每组4个重复，分别饲喂对照组和添加二氯醋酸盐（DCA）的对照组8周。结果表明，与对照组相比，添加DCA显著降低了大口黑鲈的肝体指数、肝脏和血清中的甘油三酯以及肝脏总脂质。此外，与对照组相比，DCA处理显著下调与脂肪生成相关的基因表达。此外，补充DCA显著降低了pdk 3a的mRNA表达，增加了PDHE 1 α的活性。此外，补充DCA改善了肝脏中的葡萄糖氧化性催化分解和丙酮酸氧化磷酸化（OXPHOS），这可以通过肝脏中的低丙酮酸含量以及糖酵解相关和TCA循环/OXPHOS相关基因的上调表达来证明。此外，与对照组相比，DCA摄入降低了肝脏丙二醛（MDA）含量，增强了超氧化物歧化酶（SOD）活性，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（sod 1）基因表达。这项研究表明，DCA抑制PDKs促进葡萄糖利用，减少肝脏脂质沉积，并通过增加丙酮酸OXPHOS改善大口黑鲈的氧化应激。本研究结果有助于理解PDKs-PDHE 1 α轴在葡萄糖代谢中的潜在机制，并提高养殖肉食性鱼类对饲料碳水化合物的利用率。
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 ofpdk3aand 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.