Regulatory role of quercetin, cinnamaldehyde, and glycerol monolaurate complex on lipid metabolism and antiviral mechanisms against white spot syndrome virus in Penaeus vannamei

This study investigated the distinct regulatory effects of a novel complex feed additive (quercetin: cinnamaldehyde: glycerol monolaurate = 1:1:2) on lipid metabolism, immune response, and antiviral defense in Penaeus vannamei (initial weight of 0.40 ± 0.13 g). During a 42-day feeding trial, both 0.1 % and 0.2 % complex feed additive (CFA)-supplemented groups modulated hepatopancreatic lipid metabolism by co-regulating the constitutive co-activator of PPARγ (CCPG) and the PI3K-AKT and PTGS2 pathways, promoting lipolysis, suppressing lipid synthesis, and significantly reducing lipid accumulation in the body and plasma ( P  < 0.05). CFA also activated the JAK-STAT pathway and specifically modulated the NF-κB and p38 MAPK-AP-1 pathways, significantly improving the hemocyte count (THC) and phagocytic activity (PA), and upregulating the expression of antimicrobial peptides and lysozyme, while suppressing inflammatory factors (TNFα, IL16) in both hemocytes and the intestine ( P  < 0.05). Moreover, CFA improved gut microbiota composition, with key differential genera positively correlating with host immune indices. Under white spot syndrome virus (WSSV) challenge, CFA significantly inhibited viral replication and infection ( P  < 0.05), thereby enhancing antiviral efficacy and improving shrimp survival, with the best results observed at the 0.2 % concentration. Collectively, this study demonstrates that dietary supplementation with 0.2 % CFA effectively regulates lipid metabolism and strengthens both innate and antiviral immunity in P. vannamei , providing mechanistic insights into host-pathogen interactions and the development of antibiotic alternatives for sustainable aquaculture.