Dietary valine modulates hepatic immune responses in largemouth bass (Micropterus salmoides) against Aeromonas veronii infection: Integrated regulation of antioxidant defense, ER stress and autophagy

Abstract

Largemouth bass (Micropterus salmoides) is an economically important aquaculture species in China. Aeromonas veronii (A. veronii), a conditional pathogen, causes substantial economic losses in largemouth bass farming. Valine (Val), an essential amino acid for fish, plays a crucial role in the growth of largemouth bass; however, its effects on liver health under A. veronii infection remain unclear. This study investigated the influence of dietary Val on hepatic antioxidant capacity, inflammatory response, apoptosis, and autophagy in largemouth bass following A. veronii challenge. A total of 720 juveniles (37.99 ± 0.01 g) were fed six isonitrogenous diets with graded levels of Val (11.0–26.1 g/kg diet) for 11 weeks, and the fish were subjected to a 7 d challenge trial with A. veronii. Results showed that dietary Val supplementation (20.1 g/kg) effectively mitigated A. veronii-induced histopathological damage, notably attenuating both necrotic changes and inflammatory infiltration. Mechanistically, dietary Val enhanced hepatic antioxidant capacity by activating the Nrf2/Keap1 pathway, significantly increasing antioxidant enzyme activities (SOD1, CAT, GST, GPx, GR, GCLC) and reducing oxidative stress markers (ROS, MDA, PC) (P < 0.05); Dietary Val attenuated apoptosis through downregulation of endoplasmic reticulum (ER) stress markers (GRP78, ATF6, IRE1, PERK, eIF2α, ATF4, CHOP) and modulation of Bcl2/Bax ratio (P < 0.05); Dietary Val suppressed excessive autophagy as evidenced by decreased expression of key autophagy-related genes (ULK1, ATG9, BECN1, ATG7, ATG5, LC3) and proteins (P < 0.05). Dietary Val regulated inflammatory responses by suppressing pro-inflammatory cytokines (TNF-α, IL-1β) while promoting anti-inflammatory factors (TGF-β2, IL-10). These findings demonstrate Val's multifaceted hepatoprotective effects through coordinated regulation of oxidative stress, apoptosis and autophagy pathways in A. veronii-infected largemouth bass.