Hypoxia tolerance in fish depends on catabolic preference between lipids and carbohydrates

Hypoxia is a common environmental stress factor in aquatic organisms, which varies among fish species. However, the mechanisms underlying the ability of fish species to tolerate hypoxia are not well known. Here, we showed that hypoxia response in different fish species was affected by lipid catabolism and preference for lipid or carbohydrate energy sources. Activation of biochemical lipid catabolism through peroxisome proliferator-activated receptor alpha (Pparα) or increasing mitochondrial fat oxidation in tilapia decreased tolerance to acute hypoxia by increasing oxygen consumption and oxidative damage and reducing carbohydrate catabolism as an energy source. Conversely, lipid catabolism inhibition by suppressing entry of lipids into mitochondria in tilapia or individually knocking out three key genes of lipid catabolism in zebrafish increased tolerance to acute hypoxia by decreasing oxygen consumption and oxidative damage and promoting carbohydrate catabolism. However, anaerobic glycolysis suppression eliminated lipid catabolism inhibition-promoted hypoxia tolerance in adipose triglyceride lipase (atgl) mutant zebrafish. Using 14 fish species with different trophic levels and taxonomic status, the fish preferentially using lipids for energy were more intolerant to acute hypoxia than those preferentially using carbohydrates. Our study shows that hypoxia tolerance in fish depends on catabolic preference for lipids or carbohydrates, which can be modified by regulating lipid catabolism.低氧是水生生物常见的环境胁迫，不同鱼类对低氧应激的耐受性存在着差异。然而，不同鱼类对低氧耐受性的差异机制尚未完全揭晓。该研究发现鱼类对脂肪和碳水化合物作为能量来源的偏好性会影响其对低氧应激的耐受性。实验结果显示，激活过氧化物酶体增殖物激活受体α（Pparα）或增加线粒体脂肪酸氧化可增加罗非鱼对脂肪的分解并减少对碳水化合物的分解，从而加剧了氧气消耗和氧化损伤，导致罗非鱼对急性低氧的耐受性下降。相反，抑制脂肪酸进入罗非鱼线粒体或分别敲除斑马鱼三个脂肪分解关键基因，可显著抑制实验鱼对脂肪的分解效率并促进对碳水化合物的分解，降低了实验鱼的氧气消耗和氧化损伤，从而提高实验鱼对急性低氧的耐受性。然而，在脂肪甘油三酯脂肪酶（atgl）敲除的斑马鱼中，抑制无氧糖酵解消除了由抑制脂肪分解所产生的耐受低氧的表型。随后，该研究使用不同营养级和分类地位的14种鱼进行了低氧耐受性比较实验，进一步确认了优先使用脂质作为能量来源的鱼类要比优先使用碳水化合物的鱼类更不耐受急性低氧。由此，该研究表明，不同鱼类对低氧耐受性的差异至少部分取决于其对脂肪或碳水化合物分解代谢的偏好性；而在同种鱼类中，可以通过调控脂肪分解代谢效率来改变其对低氧的耐受性。.