Conjugated linoleic acid

Conjugated linoleic acid (CLA) isomers have been reported to reduce body weight and promote glycolipid metabolism in animals. In a preliminary study, we revealed that trans-10, cis-12-CLA (10,12-CLA) plays an important role in modulating lipid metabolism in chickens. However, the underlying mechanism remains unclear. In this study, we constructed an isolated in vitro model with primary chicken hepatocytes to investigate the effect of 10,12-CLA on lipid metabolism. 10,12-CLA inhibited lipid accumulation by decreasing the mRNA expression of sterol regulatory element-binding protein-1c (SREBP-1c), SREBP2, 3‑hydroxy-3-methylglutaryl-CoA reductase (HMGCR), fatty acid synthase (FAS), adipose triacylglyceride lipase (ACC), and lipoprotein lipase (LPL) and increasing the mRNA expression of peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyltransferase 1 (CPT1) and adipose triacylglyceride lipase (ATGL). Furthermore, 10,12-CLA treatment activated the protein expression of extracellular signal-regulated kinase 1/2 (ERK1/2) and AMP-activated protein kinase (AMPK), whereas treatment with the ERK1/2 inhibitor U0126 reversed the inhibitory effects of 10,12-CLA on lipid accumulation by blocking the ERK1/2-AMPK pathway, leading to increased lipid accumulation and triglyceride content in primary chicken hepatocytes. These findings suggest that in chicken hepatocytes, 10,12-CLA alleviates hepatocyte lipid deposition by activating the ERK1/2-AMPK pathway, promoting fatty acid oxidation and reducing lipid synthesis, revealing the potential mechanism through which 10,12-CLA regulates hepatic lipid metabolism in chickens.

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.