A new strategy: Dietary lipids protected the liver from hypoxia injury in multiple ways in grass carp (Ctenopharyngodon idella)

Hypoxia is becoming a non-negligible issue in aquaculture. The studies of dietary lipids mainly focused on growth performance, immune and meat quality of fish. There were scarce reports that dietary lipids can help fish resist stress, especially hypoxia stress. The objective of this study was to investigate the effects of dietary lipids on hypoxia-caused liver injury, oxidative damage, apoptosis, endoplasmic reticulum (ER) stress and autophagy of grass carp (Ctenopharyngodon idella), as well as make sure the lipid requirement of grass carp to resist hypoxia. Grass carp were fed diets containing six graded lipid levels (0%, 1.2%, 2.4%, 3.6%, 4.8% and 6.0%) for 60 days and exposed to hypoxia or normoxia for 96 h respectively. As shown in our results of grass carp, diets with proper lipid levels relieved hypoxia-induced adverse effects: (1) alleviated liver injury [decreased lactic dehydrogenase (LDH), glutamic oxalacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) activity, as well as reduced hepatic cellular vacuolation (HCV) and improved ER morphology]; (2) diminished liver oxidative damage [decreased reactive oxygen species (ROS), malondialdehyde (MDA) and protein carbonyl (PC) contents] and inhibited liver apoptosis (decreased caspase-3, −8 and − 9 activity); (3) relieved liver ER stress which might have connection with the inhibition of glucose regulated protein 78 (GRP78) -protein kinase R-1ike ER kinase (PERK) - eukaryotic translation initiation factor 2 subunit alpha (eIF2α) - activating transcription factor 4 (ATF4) and GRP78 - activating transcription factor 6 (ATF6) - X-box binding protein 1 (XBP1) pathways, rather than inhibition of inositol-requiring kinase1α (IRE1) pathway; (4) inhibited liver autophagy which might be related to the inhibition of the initiation [unc-51 like autophagy activating kinase 1 (ULK1)], elongation and closure [autophagy-related protein 5 (ATG5), autophagy-related protein 12 (ATG12) and light chain3II protein (LC3II)] of autophagosomes, rather than the inhibition of mitophagy and sequestosome 1 (P62) mediated degradation of substrates. In all, diets with proper lipid levels might be helpful to relieve hypoxia-induced adverse effects (injury, oxidative damage, apoptosis, ER stress and autophagy in the liver) on grass carp. Based on ROS and MDA contents of grass carp liver, we determined the optimal lipid levels to resist hypoxia-induced liver damage were 3.59% and 3.05%, respectively.