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

BACKGROUND

Fish oil (FO), rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), exerts beneficial effects on gastrointestinal diseases in humans and animals.

OBJECTIVES

This study aimed to investigate whether FO attenuated deoxynivalenol (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 FO) and DON exposure (4 mg/kg DON or not). After 21 d of feeding, intestinal samples were collected. Intestinal porcine epithelial cell line 1 (IPEC-1) cells were treated with 41 μM EPA or 38 μM DHA, with or without 0.5 μg/mL DON. Small interfering RNAs 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

FO 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, mitochondrial dysfunction, and 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, mitochondrial dysfunction, and cell apoptosis (P < 0.001) in the presence of siDrpl and siMfnl; however, EPA or DHA could not alleviate these indices (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.