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Article Abstract
Conjugated linoleic acid (CLA) is a natural bioactive compound with antioxidant, anti-inflammatory, and antibacterial properties. This study investigated the dose-dependent effects of dietary CLA on oxidative stress (OS), inflammatory response and apoptosis in black seabream (Acanthopagrus schlegelii). Four isonitrogen and isolipid diets were formulated with graded levels of CLA: 0 % (CLA0), 0.5 % (CLA0.52), 1.0 % (CLA1.09), 2.0 % (CLA2.29). The results showed that moderate dietary CLA supplementation (1.09 %) significantly enhanced hepatic antioxidant capacity by upregulating Kelch-like ECH-associated protein 1 (Keap1) and downstream antioxidant genes, indicating activation of the Keap1/nuclear factor E2-related factor 2 (Nrf2) pathway. In contrast, high CLA levels (2.29 %) markedly activated Nrf2 and heme oxygenase-1 (Ho-1), promoted Nrf2 nuclear translocation but paradoxically suppressed its downstream targets, accompanied by elevated reactive oxygen species (ROS) levels, suggesting dysregulated antioxidant responses. Excessive CLA (2.29 %) also induced a pro-inflammatory state, evidenced by nuclear translocation of nuclear factor κB (NF-κB) p65, upregulation of pro-inflammatory cytokines, and suppression of anti-inflammatory cytokines, indicating a pronounced pro-inflammatory response, while low to moderate CLA had no such effect. Furthermore, high-dose CLA (2.29 %) activated the c-Jun N-terminal kinase (JNK) pathway, upregulated expression of pro-apoptotic genes, and reduced anti-apoptotic B cell lymphoma 2 (bcl-2) expression, indicating enhanced hepatocyte apoptosis. Collectively, these findings demonstrate that dietary CLA exerts dose-dependent immunomodulatory effects in A. schlegelii through Keap1/Nrf2 and NF-κB signaling pathways, with 1.09 % CLA offering antioxidant benefits, whereas excessive levels (2.29 %) induce oxidative stress, inflammation, and apoptosis.
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| http://dx.doi.org/10.1016/j.fsi.2025.110603 | DOI Listing |
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