Abstract
Nonalcoholic fatty liver disease (NAFLD) is common in farmed fish fed a high-fat diet (HFD), which disrupts lipid metabolism, inhibits growth performance, and poses a serious threat to sustainable aquaculture. This study explored the anti-NAFLD effect and hepatoprotective mechanism of YZW-A, a water-soluble heteroglycan extracted from the pomelo fruitlet (Citrus maxima), in hybrid grouper (Epinephelus lanceolatus♂ × Epinephelus fuscoguttatus♀). Hybrid grouper were fed an HFD, with 15% lipid, supplemented with YZW-A for 56 days. In vivo, addition of YZW-A resulted in improved growth performance and feed utilization, while it reduced whole body and muscle lipid content, viscerosomatic and hepatosomatic indexes, and lipid deposition in the hepatocytes. Lipogenesis-related genes were downregulated while lipolysis-related genes were upregulated in grouper supplemented with YZW-A. Additionally, destructive morphological changes in the liver tissue cells detected in HFD-fed grouper were normalized after treatment with YZW-A. In vitro, YZW-A improved lipid emulsion-induced hepatic steatosis by modulating key factors of lipid metabolism, achieved by triggering the AMP-activated protein kinase (AMPK) pathway in the hepatocytes and activating the AMPK/Nrf2/ARE axis. These results demonstrated the therapeutic effect of YZW-A on diet-induced NAFLD in hybrid grouper and elucidated a possible mechanism underlying NAFLD prevention and suppression of further deterioration by YZW-A.