Arctigenin

The intestinal mucosal barrier is fundamental to fish health and nutrient utilization. L-arginine (Arg) is a multifunctional amino acid and essential for maintaining intestinal integrity, yet its mechanisms, particularly concerning redox homeostasis and inter-organelle communication, remain unclear. Using a grass carp model, we investigated the effects of Arg deficiency and supplementation on intestinal barrier function, focusing on mitochondrial function and endoplasmic reticulum (ER) stress. This study reveals that Arg deficiency damaged the intestinal physical barrier, as evidenced by impaired morphology and reduced expression of tight junction proteins. Conversely, Arg supplementation significantly enhanced barrier integrity and digestive enzyme activity. This protective effect was achieved through two possible mechanisms: 1) Arg improving mitochondrial function by enhancing oxidative phosphorylation (OXPHOS) and promoting the mitochondrial quality control system, leading to elevated ATP production and a significant reduction in reactive oxygen species (ROS) levels. 2) Improving ER stress and facilitating organelle crosstalk: Arg supplementation mitigated ER stress and strengthened the physical and functional interaction at mitochondria-associated membranes (MAMs). This may be driven by the upregulation of calcium (Ca²⁺) transporters and MAM-associated proteins, which helped stabilize intracellular Ca²⁺ signaling and reduce apoptosis. Our findings suggest a potential role of Arg enhances intestinal barrier function by regulating the health of mitochondria and endoplasmic reticulum and coordinating the interactions mediated by mitochondrial-associated membranes (MAMs). This study underscores the critical role of redox balance and organelle interaction in maintaining intestinal homeostasis and positions Arg as a key nutrient for improving health in fish.