Regulative Effect Of Asparagine On Liver Injury And Muscle Protein Degradation Of Piglets After Lipopolysaccharide Challenge

These experiments were conducted to e valuate the regulative role ofasparagine (Asn) on liver injury and muscle protein degradation of pigletsafter lipopolysaccharide (LPS) challenge and its mechanis ms.1. This experime nt was conducted to investigate whether Asn couldalleviate LPS-induced liver injury in piglets via modulat ion of TLR4andNOD signaling pathways. Forty-eight pigs were allotted to fourtreatment s including:1) control group (basal diet);2) LPS group (basaldiet+LPS);3)0.5%Asn group (basa l diet+0.5%Asn+LPS);4)1.0%Asn group (basal diet+1.0%Asn+LPS). After20d feedi ng with c ontrol(0%Asn),0.5%or1.0%Asn supple me nted diets, pigs wer e injected wit hsaline or LPS. At4(early phase) and24h (late phase) post-injection,blood and liver sa mples were obtained. The resul ts showed that:(1) Asnattenuated liver injury indicated by lower serum aspartatea minotransferase a nd alkaline phos phatase activity, and higher serumalanine aminotransferase/aspartate aminotransferase ratio and liverclaudin-1protein expression at24h post-injection (P<0.05).(2) Asndecreased mRNA e xpressions of liver tumor ne crosis fac tor-α (TNF-α)and heat shock protein70at4h pos t-injection, and increased mRNAexpression of TNF-α at24h post-injection (P<0.05).(3) Asn decr easedmRNA expressions of liver TLR4, IL-1receptor-associated kinase1(IRAK1), TNF-α r eceptor-associated factor6(TRAF6), NOD1, NOD2,receptor-interacting serine/threonine-protein kinase2(RIPK2) andnuclear factor-κB (NF-κB) at4h post-injection, and increased mRNAexpressions of liver TLR4, myeloid differentiation factor88(MyD88),IRAK1, NOD2at24h post-injection (P<0.05).(4) Asn increased mRNAexpressions of liver single i mmunoglobulin IL-1R-related molecule(SIGIRR) and centaurin β1(ACAP1) at24h post-injection (P<0.05). These results indicate that at early and late phases of LPS challenge, Asnexerts opposite regulatory effects on mRNA expression of he paticpro-inflammatory cytokines and TLR4and NOD signaling pathway, andi mproves liver integrity.2. This experime nt was conducted to investigate whether Asn couldalleviate LPS-induced muscle protein degr adation in piglets viamodulation of AM PK, Akt/FOXO, TLR4and NOD signaling pathways.Twenty-four pigs were allotted to four treatme nts including:1) controlgroup (ba sal diet);2) LPS group (basa l diet+LPS);3)0.5%Asn group(basal diet+0.5%Asn+LPS);4)1.0%Asn group (basal diet+1.0%Asn+LPS). After19d feeding with control (0%Asn),0.5%or1.0%Asnsupple me nted diets, pigs were inje cted with saline or LPS. At4post-injection, mus cle samples were obtained. The results showed that:(1)0.5%Asn increased mu scle protein mass indicated by higher protein andDNA c ontents, RNA/DNA a nd protei n/DNA ra tios in ga strocne mius andlongissi mus dorsi (P<0.05).(2) Asn decreased mRNA expressions ofatrophy F-box and muscle RING fi nger1in gastrocne mius andlongissi mus dorsi (P<0.05).(3) Asn decreased AMPKα phosphoryl ationand increased Akt phosphorylation in gastrocne mius a nd longis si musdorsi, and increased FOXO1phos phor ylation in longissi mus dorsi(P<0.05).(4) Asn decreased mRNA expressions of TLR4, MyD88, TRAF6,NOD1, NOD2, NF-κB, and T NF-α in gastrocne mius and longissi mus dorsi(P<0.05).(5) Asn decreased mRNA e xpressions of radioprotective105,suppressor of cytokine signaling1(SOCS1) and ACAP1in gastrocnemiusand longi ssi mus dorsi (P<0.05). The se results indicate that Asn ma ysuppress muscle pr o-infla mmatory cytokine production via regulation ofTLR4and NOD signaling pat hways, and therefor e i mprove muscle pr oteinmass, pos sibly through maint enance of AMPK, a nd Akt/FOXO signalings.