Fish are poor users of dietary carbohydrates and often display prolonged hyperglycemia and fat deposition after feeding high digestible carbohydrate diets. Recently, fatty acid β-oxidation (FAO) inhibition has been reported to increase glucose oxidation in fish. Therefore, this study tested the assumption that the inhibition of FAO with mildronate (MD, a carnitine synthesis inhibitor) might also increase glucose utilization and alleviate adverse effects induced by high starch diet (HSD) in Nile tilapia, Oreochromis niloticus. Nile tilapia juveniles (6.13 ± 0.11 g) were cultured in nine 200-L tanks (30 fish per tank) and divided into three groups (three tanks per group). The fish were fed twice a day (9:00 and 18:30) at 4% body weight by using a normal starch diet (NSD, 30% corn starch), a HSD (45% corn starch), or a HSD supplemented with MD (25 g/kg of diet, HSD + MD) for eight weeks. These three feeds contained approximately 35.8% protein and 6.4% lipid. The fish each tank were weighed every two weeks, and the feeding amount was adjusted accordingly. After the feeding trial, the fish fed on HSD showed higher hepatosomatic index (HSI), visceral somatic index (VSI), serum triglyceride concentration and whole-body and tissue (liver and muscle) lipid contents than those fed on NSD. The fish fed on HSD also had higher relative area of vacuolation in the liver, hepatic malondialdehyde (MDA) content, and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities in the serum than those fed on NSD. Moreover, the fish fed on HSD increased serum glucose and insulin concentrations, and hepatic lactate, pyruvate and glycogen contents, but reduced whole-body protein content and dietary protein utilization than those fed on NSD, indicating that HSD induced fat deposition, liver damage, glucose intolerance and lowered protein-sparing effect. However, the fish fed on HSD + MD decreased hepatic carnitine content and FAO activity, attenuated the indexes related to fat deposition and liver damage, improved blood glucose clearance and whole-body protein deposition than those fed on HSD, suggesting that the adverse effects caused by HSD were reversed after FAO inhibition. Furthermore, the fish fed on HSD down-regulated the expression of genes associated with glucose uptake, glycolysis, FAO process, and lipolysis compared to those fed on HSD + MD and NSD, yet up-regulated lipogenic and proteolytic genes. These data suggested that inhibition of FAO improved glucose utilization and alleviated the HSD-induced adverse effects in Nile tilapia. This work demonstrates that, modifying mitochondrial FAO activity regulates the ability of fish to adapt to HSD intake through remodeling energy homeostasis. Our study provides new insights into improving carbohydrate utilization in aquatic animals.

鱼是饮食中碳水化合物的贫穷使用者，在喂食高消化性碳水化合物的食物后，经常表现出长时间的高血糖症和脂肪沉积。最近，据报道，脂肪酸β-氧化（FAO）抑制可增加鱼类的葡萄糖氧化。因此，本研究中测试的假设是FAO的抑制与mildronate（MD，肉碱合成抑制剂）也可能会增加葡萄糖的利用和减轻由高淀粉饮食（HSD）在尼罗罗非鱼，诱发的不良影响尼罗罗非鱼。尼罗罗非鱼幼鱼（6.13±0.11 g）在9个200公升的水箱中养殖（每箱30条鱼），分为三组（每组三箱）。通过使用普通淀粉饮食（NSD，30％玉米淀粉），HSD（45％玉米淀粉）或补充了HSD的HSD，每天以4％的体重喂鱼两次（9:00和18:30） MD（25 g / kg饮食，HSD + MD）八周。这三种饲料含有大约35.8％的蛋白质和6.4％的脂质。每两周称重每个鱼缸的鱼，并相应地调整喂食量。投喂试验后，以HSD饲喂的鱼比以NSD饲喂的鱼显示出更高的肝体指数（HSI），内脏躯体指数（VSI），血清甘油三酸酯浓度以及全身和组织（肝脏和肌肉）脂质含量。用HSD喂养的鱼肝脏中的空泡相对面积也较高，血清丙二醛（MDA）含量，血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）活性均高于NSD。此外，饲喂HSD的鱼比饲喂NSD的鱼增加了血清葡萄糖和胰岛素浓度，以及肝乳酸，丙酮酸和糖原的含量，但降低了人体蛋白质含量和饮食蛋白质的利用率，这表明HSD会引起脂肪沉积，肝脏损害，葡萄糖不耐症和降低蛋白保存的作用。然而，饲喂HSD + MD的鱼比饲喂HSD的鱼减少了肝肉碱含量和FAO活性，减弱了与脂肪沉积和肝损伤有关的指标，改善了血糖清除率和全身蛋白质沉积，表明这种不良反应引起在粮农组织抑制之后，HSD的研究被逆转。此外，与饲喂HSD + MD和NSD的鱼相比，饲喂HSD的鱼下调了与葡萄糖摄取，糖酵解，FAO过程和脂解相关的基因的表达，但上调了脂肪生成和蛋白水解基因。这些数据表明，抑制FAO可以提高葡萄糖利用率，并减轻HSD引起的尼罗罗非鱼的不良反应。这项工作表明，改变线粒体的粮农组织活动可以通过重塑能量稳态来调节鱼类适应HSD摄入的能力。我们的研究为改善水生动物的碳水化合物利用提供了新见解。这些数据表明，抑制FAO可以提高葡萄糖利用率，并减轻HSD引起的尼罗罗非鱼的不良反应。这项工作表明，改变线粒体的粮农组织活动可以通过重塑能量稳态来调节鱼类适应HSD摄入的能力。我们的研究为改善水生动物的碳水化合物利用提供了新见解。这些数据表明，抑制FAO可以提高葡萄糖利用率，并减轻HSD引起的尼罗罗非鱼的不良反应。这项工作表明，改变线粒体的粮农组织活动可以通过重塑能量稳态来调节鱼类适应HSD摄入的能力。我们的研究为改善水生动物的碳水化合物利用提供了新见解。