Mitochondrial Fusion Protein Mitofusin-2 Mediates the Protection of Fish Oil Against Porcine Intestinal Injury Induced by Deoxynivalenol.

BACKGROUND: Fish oil, rich in EPA and DHA, exerts beneficial effects on gastrointestinal diseases in humans and animals. OBJECTIVE: This study aimed to investigate whether fish oil attenuated DON-induced intestinal dysfunction and abnormal expression of mitochondrial fission/fusion-related proteins in weaned piglets. METHODS: Twenty-four weaned pigs were used in a 2 × 2 factorial design (6 pigs /group) and the factors included dietary treatments (5% corn oil or fish oil) and DON exposure (4 mg/kg DON or not). After 21 d feeding, intestinal samples were collected. IPEC-1 cells were treated with 41 μM EPA or 38 μM DHA, with or without 0.5 μg/mL DON. siRNA targeting mitochondrial fission/fusion-related proteins (dynamin-related protein 1 (Drp1), mitofusin-1 (Mfn1) and mitofusin-2 (Mfn2)) were used to explore the molecular mechanism. RESULTS: Fish oil improved growth performance (P < 0.05) and increased expression of mitochondrial fission/fusion-related proteins including Drp1, Mfn1, and Mfn2 (P < 0.05), accompanied by restoring jejunal morphology, digestion, and barrier function, and mitochondrial function (P < 0.05) of piglets after DON exposure. EPA or DHA attenuated cell damage, mitochondria dysfunction, cell apoptosis (P < 0.001), and increased Drp1, Mfn1 and Mfn2 protein expression (P < 0.05) after DON exposure in IPEC-1 cells. EPA/DHA alleviated cell injury, mitochondria dysfunction and cell apoptosis (P < 0.001) in the presence of siDrp1 and siMfn1, however EPA or DHA could not alleviate these indexes (P > 0.05) in the presence of siMfn2. CONCLUSIONS: The protective effects of EPA/DHA against DON-induced intestinal injury were strongly associated with Mfn2 signaling.