Lactobacillus delbrueckii alleviates lipopolysaccharide‐induced muscle inflammation and atrophy in weaned piglets associated with inhibition of endoplasmic reticulum stress and protein degradation

Abstract

AbstractPro‐inflammatory cytokines in muscle play a pivotal role in physiological responses and in the pathophysiology of inflammatory disease and muscle atrophy. Lactobacillus delbrueckii (LD), as a kind of probiotics, has inhibitory effects on pro‐inflammatory cytokines associated with various inflammatory diseases. This study was conducted to explore the effect of dietary LD on the lipopolysaccharide (LPS)—induced muscle inflammation and atrophy in piglets and to elucidate the underlying mechanism. A total of 36 weaned piglets (Duroc × Landrace × Large Yorkshire) were allotted into three groups with six replicates (pens) of two piglets: (1) Nonchallenged control; (2) LPS‐challenged (LPS); (3) 0.2% LD diet and LPS‐challenged (LD+LPS). On d 29, the piglets were injected intraperitoneally with LPS or sterilized saline, respectively. All piglets were slaughtered at 4 h after LPS or saline injection, the blood and muscle samples were collected for further analysis. Our results showed that dietary supplementation of LD significantly attenuated LPS‐induced production of pro‐inflammatory cytokines IL‐6 and TNF‐α in both serum and muscle of the piglets. Concomitantly, pretreating the piglets with LD also clearly inhibited LPS‐induced nuclear translocation of NF‐κB p65 subunits in the muscle, which correlated with the anti‐inflammatory effects of LD on the muscle of piglets. Meanwhile, LPS‐induced muscle atrophy, indicated by a higher expression of muscle atrophy F‐box, muscle RING finger protein (MuRF1), forkhead box O 1, and autophagy‐related protein 5 (ATG5) at the transcriptional level, whereas pretreatment with LD led to inhibition of these upregulations, particularly genes for MuRF1 and ATG5. Moreover, LPS‐induced mRNA expression of endoplasmic reticulum stress markers, such as eukaryotic translational initiation factor 2α (eIF‐2α) was suppressed by pretreatment with LD, which was accompanied by a decrease in the protein expression levels of IRE1α and GRP78. Additionally, LD significantly prevented muscle cell apoptotic death induced by LPS. Taken together, our data indicate that the anti‐inflammatory effect of LD supply on muscle atrophy of piglets could be likely regulated by inhibiting the secretion of pro‐inflammatory cytokines through the inactivation of the ER stress/NF‐κB singling pathway, along with the reduction in protein degradation.