High protein intake promotes the adaptation to chronic hypoxia in zebrafish (Danio rerio)

Chronic hypoxia is a common environmental stress factor in aquaculture. Many researchers have illustrated the physiological and metabolic changes under chronic hypoxia, but there are few studies to evaluate the relationship between dietary nutrients and hypoxic adaptation in fish. In the present study, we fed zebrafish with control diet (C), high-carbohydrate diet (HC), high-fat diet (HF) and high-protein diet (HP) at normal dissolved oxygen (DO = 7.0 ± 0.5 mg/L) or low dissolved oxygen (DO = 2.5 ± 0.5 mg/L) environment, respectively. After a 7-week feeding trial, the growth performance, body composition, tissue biochemical indexes, mRNA expressions of hifα isoforms and nutrient metabolism-related genes, intestinal digestive enzyme activities and microbiota composition were measured. The results indicated that only the HP diet could alleviate the reduction of body weight and feed efficiency induced by chronic hypoxia, but the HF diet feeding worsened the adverse effects of chronic hypoxia in zebrafish. At the C groups, hypoxia increased catabolism of lipid and protein, but at the HP groups, hypoxia enhanced utilization of glycogen and protein. Compared to the C-hypoxia group, the HP feeding could activate transcription of hif-1a and its downstream glycolysis genes in chronic hypoxia. Furthermore, at hypoxic state, the HP feeding could alleviate the reduction of intestinal digestive enzyme activities and microbiota dysbiosis induced by the chronic hypoxia, including increasing bacterial diversity and decreasing Cetobacterium genus abundance. This is the first study indicating that high protein intake could strengthen ability of fish in resisting the negative effect of chronic hypoxia.