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This study was conducted to explore the effect of dietary LD on the lipopolysaccharide (LPS)\u2014induced muscle inflammation and atrophy in piglets and to elucidate the underlying mechanism. A total of 36 weaned piglets (Duroc \u00d7 Landrace \u00d7 Large Yorkshire) were allotted into three groups with six replicates (pens) of two piglets: (1) Nonchallenged control; (2) LPS\u2010challenged (LPS); (3) 0.2% LD diet and LPS\u2010challenged (LD+LPS). On d 29, the piglets were injected intraperitoneally with LPS or sterilized saline, respectively. All piglets were slaughtered at 4\u2009h 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\u2010induced production of pro\u2010inflammatory cytokines IL\u20106 and TNF\u2010\u03b1 in both serum and muscle of the piglets. Concomitantly, pretreating the piglets with LD also clearly inhibited LPS\u2010induced nuclear translocation of NF\u2010\u03baB p65 subunits in the muscle, which correlated with the anti\u2010inflammatory effects of LD on the muscle of piglets. Meanwhile, LPS\u2010induced muscle atrophy, indicated by a higher expression of muscle atrophy F\u2010box, muscle RING finger protein (MuRF1), forkhead box O 1, and autophagy\u2010related 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\u2010induced mRNA expression of endoplasmic reticulum stress markers, such as eukaryotic translational initiation factor 2\u03b1 (eIF\u20102\u03b1) was suppressed by pretreatment with LD, which was accompanied by a decrease in the protein expression levels of IRE1\u03b1 and GRP78. Additionally, LD significantly prevented muscle cell apoptotic death induced by LPS. Taken together, our data indicate that the anti\u2010inflammatory effect of LD supply on muscle atrophy of piglets could be likely regulated by inhibiting the secretion of pro\u2010inflammatory cytokines through the inactivation of the ER stress\/NF\u2010\u03baB singling pathway, along with the reduction in protein degradation.\n                  <\/jats:p>","DOI":"10.1096\/fj.202400969rr","type":"journal-article","created":{"date-parts":[[2024,9,9]],"date-time":"2024-09-09T11:36:38Z","timestamp":1725881798000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["<i>Lactobacillus delbrueckii<\/i>\n                    alleviates lipopolysaccharide\u2010induced muscle inflammation and atrophy in weaned piglets associated with inhibition of endoplasmic reticulum stress and protein degradation"],"prefix":"10.1096","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4125-9840","authenticated-orcid":false,"given":"Songshi","family":"Zhong","sequence":"first","affiliation":[{"name":"College of Animal Science and Technology Hunan Agricultural University  Changsha P.R. 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