Lauric acid ameliorates excessive linoleic acid induced macrophage inflammatory response and oxidative stress in large yellow croaker (Larimichthys crocea)

Abstract

Macrophages are particularly prone to inflammation and oxidative stress upon exogenous stimulus. Previous investigations have shown that lauric acid (LRA) exerts anti-inflammatory and antioxidant effects, however, the molecular mechanism remains elusive. This study aims to elucidate the function and molecular mechanisms by which LRA provided a defense against inflammation and oxidative stress brought by linoleic acid (LA), both in vivo and in vitro. Feeding trial results indicated that dietary LA led to severe inflammation and impaired antioxidant capacity in head kidney of large yellow croaker. The gene and protein expressions of inflammation-related were upregulated and those of antioxidant defense were down-regulated in the LA diet group, which were reversed by glycerol monolaurate (LRA derivative). Meanwhile, in macrophages, LRA suppressed the expressions of p-ERK and p-JNK and the gene expressions of pro-inflammatory factors induced by excessive LA. G protein coupled receptor 84 (GPR84, endogenous receptor of LRA) disturbance did not alter LRA-induced ERK and JNK MAPK pathways and pro-inflammatory gene expressions decline. Besides, LRA decreased reactive oxygen species (ROS) level and increased the expressions of nuclear factor erythroid 2-related factor 2 (NRF2). And blockage of NRF2 reversed the protective effect of LRA-mediated the protection against oxidative stress. Collectively, these results demonstrated that LRA attenuated LA-induced inflammation by suppressing ERK and JNK MAPK pathways and oxidative stress by activating NRF2 signaling in macrophages. These findings revealed that the function and molecular mechanisms of LRA alleviating inflammation and oxidative stress in macrophages, which provides new insights for enhancing immune cell function in vertebrates.