Flaxseed Oil Attenuates Intestinal Damage by Regulating Ferroptosis Signaling Pathway Following LPS Challenge in Piglets.

Abstract

Ferroptosis has been demonstrated to play an important role in various tissue injuries and diseases. Flaxseed oil (FO) has been proven to have benefits for intestinal health. This study aims to explore whether FO relieved lipopolysaccharide (LPS)-induced intestinal injury through modulating ferroptosis signaling pathway. A total of 120 weaned piglets are fed diets with 3% soybean oil (SO) or 3% FO for 4 weeks. At the end of the trial, 24 piglets selected from two dietary treatment groups are used in a 2 × 2 factorial design with oil treatment (3% SO versus 3% FO) and LPS challenge (saline versus LPS). At 4h postinjection with LPS, 24 piglets are slaughtered and intestinal samples are collected. FO improves growth performance of pigs. After LPS treatment, FO mitigates intestinal morphological damage and functional damage. Notably, FO reverses the typical ultra-morphology and biochemical indexes of ferroptosis involving glutathione, malondialdehyde, and 4-hydroxynonenal contents. Mechanistically, FO ameliorates the changes on mRNA or protein abundance of key ferroptosis signals including transferrin receptor protein 1 (TFR1), recombinant iron responsive element binding protein 2 (IREB2), FTL, HSPB1, ferritin heavy chain 1 (FTH1), ferroportin 1 (FPN1), SLC7A11, solute carrier family 3 member 2 (SLC3A2), glutathione peroxidase 4 (GPX4), and arachidonate-15-lipoxygenase (ALOX15). FO improves growth performance and mitigates intestinal structural and functional damage, which is involved in regulating ferroptosis signaling pathway.