Hypoxia tolerance of fish depends on the catabolic preference between lipid and carbohydrate

Hypoxia is a common environmental stress in aquatic organisms, which varies among fish species. However, the mechanism among fish species to tolerate hypoxia are not well known. Here we show that hypoxia response in different fish species is affected by lipid catabolism and preference for lipid or carbohydrate energy source. Biochemical lipid catabolism activation through activating peroxisome proliferators activated receptor alpha (Ppara) or increasing mitochondrial fat oxidation in tilapia decreased tolerance to acute hypoxia by increasing oxygen consumption and oxidative damage, and reducing carbohydrate catabolism as energy source. Conversely, lipid catabolism inhibition through suppressing entry of lipid 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 patatin-like phospholipase domain containing 2 (atgl) mutant zebrafish. In the following test using 14 fish species with different trophic levels and taxonomic status, the fish using lipid preferentially for energy source were more intolerant to acute hypoxia than those preferably utilizing carbohydrate. Our study shows that hypoxia tolerance in fish depends on catabolic preference for lipid or carbohydrate, which can be modified by regulating lipid catabolism.