Reactive oxygen species (ROS) burst as a primary driver of high-carbohydrate diet-induced metabolic liver disease in carnivorous fish

High-carbohydrate diets (HCD) induce highly consistent metabolic liver disease in carnivorous fish, commonly characterized by redox imbalance and dysregulation of glycolipid metabolism. However, the role of elevated reactive oxygen species (ROS) under oxidative stress in this pathological process remains inadequately elucidated. This study investigated the mechanism by which HCD-induced ROS burst drives liver damage in the carnivorous fish, largemouth bass (Micropterus salmoides). Through integrated physiological, biochemical, and multi-omics analyses, we found that HCD significantly elevated the liver ROS levels, inducing oxidative stress (increased malondialdehyde and suppressed antioxidant enzyme activities), mitochondrial dysfunction (reduced membrane potential, mtDNA damage, and ultrastructural disruption), and inhibition of the PINK1/Parkin-mediated mitophagy pathway. To scavenge excess ROS, the mitochondria-targeted antioxidant Mito-TEMPO was employed for intervention. The results demonstrated that the aforementioned pathological phenotypes were significantly ameliorated, and mitophagy was restored, confirming ROS burst as a core factor exacerbating HCD-induced liver damage. Furthermore, integrated transcriptomic and metabolomic analysis revealed that ROS burst and its scavenging can remodel the sphingolipid and amino acid metabolic networks, with gba2 and chac1 identified as key hub genes. These findings elucidate the central role of ROS in HCD-induced metabolic liver disease in carnivorous fish, providing insights for antioxidant-based intervention strategies against metabolic disorders in aquaculture.