Effects Of Goose Deoxycholic Acid On Hepatic Inflammation In FLHS Laying Hens

Fatty liver hemorrhagic syndrome(FLHS)is a common kind of nutrition metabolic disease in laying peak stage of hens,which exhibits many classic liver damage symptoms including hepatomegaly,hepatic fatty degeneration and bleeding,meanwhile induces significant laying performance decline and high mortality resulting in huge economic loss in laying hens breeding industry.The pathogenesis of FLHS is unclear,but it is considered to be one of the non-alcoholic fatty liver disease(NAFLD),and the two-hit hypothesis was widely recognized for the pathogenesis of NAFLD.According to the hypothesis,the first attack was the disorder of lipid metabolism in hepatocytes and abnormal accumulation of lipid in hepatocytes,while the second attack was the activation of various oxygen free radicals and inflammatory mediators,which further caused the damage of hepatocytes.Bile acid,the main component of bile,has been identified that not only plays an important role in fat metabolism,but also exhibits obvious antioxidant capacity and anti-inflammatory activity in acute and chronic inflammation.Our research group and previous studies have proved that the level of bile acid decreased significantly in experimental animals and patients with fatty liver,whereas targeted activation of bile acid-related signaling pathways has obviously preventive and therapeutic effects on the fatty liver.In the present study,FLHS layer models were induced by feeding high energy and low protein diet,at the meanwhile,chenodeoxycholine acid(CDCA,the main composition of chicken bile acid)was supplemented,then the effect of CDCA on the hepatic pathological changes,antioxidant capacity,autophagy and KC cells mediated inflammatory reaction was detected by the means of HE staining and fluorescence quantitative PCR and ELISA methods.The objective of the study was to elucidated the effect of CDCA on the hepatic inflammation of FLHS laying hens,which would provide theoretical basis for bile acids application in prevention and treatment FLHS of layers.A total of 216 Highland brown layers of 26-week-old with similar egg production rate and body weight were randomly divided into 6 groups: control group,model group,CDCA low-dose group,CDCA medium-dose group,CDCA high-dose group and CDCA control group.After 1 week of feeding,the formal trial begined and lasted for 24 weeks,and liver tissue and blood samples were collected for relevant indicators determination.The results showed:1.FLHS laying hen models were successfully induced by high energy and low protein diet.After CDCA intervention,the bleeding signs were alleviated,hepatic fat vacuoles were reduced,and serum ALT and AST contents were significantly reduced,indicating that CDCA had an obvious preventive effect on FLHS occurrence in laying hens.2.After CDCA intervention,the activities of T-SOD,CAT,GSH-Px and T-AOC in the liver were significantly increased,while the content of MDA was significantly decreased,indicating that CDCA could improve hepatic antioxidant capacity of FLHS laying hens.3.After CDCA intervention,hepatic autophagy markers LC3-Ⅰ and P62 m RNA expression levels significantly decreased,while LC3 Ⅱ and Beclin m RNA expression levels significantly increased,suggesting CDCA could alleviate hepatic autophagy inhibition of FLHS laying hens.4.After CDCA intervention,the expression levels of hepatic M1-type KCs markers i NOS and CD68 m RNA were significantly decreased;the levels of M1-type KCs polarization products including IL-1,IL-6,IL-8,IL-18,i NOS and TNF-α of were significantly decreased;the expression levels of LPS-TLR4-my D88-NF-kb signaling pathway factors including LPS,AP-1,IRF1,IRF5,Caspase-11,NF-KB,Myd88 and TLR4 m RNA were significantly decreased;the expression levels of JAK-STAT signaling factors including IFN-γ,JAK2,STAT1 and IRF5 m RNA were significantly decreased;the expression levles of pro-inflammatory regulators NLRP3,Casepase-1 and Casepase-11 m RNA were significantly decreased.The results indicated that CDCA could inhibit hepatic inflammatory reaction mediated by M1-type KCs in FLHS layers through acting on LPS-TLR4-my D88-NF-kb and JAK-STAT signaling pathways and pro-inflammatory regulators.5.After CDCA intervention,the expression levels of hepatic CD206 and CD163 m RNA,and IL-4 and IL-10 contents of M2-type KCs markers were significantly increased;whereas the expression levels of JAK-STAT pathway factors including SOCS1,ARG,IL-4R,PPAR m RNA were significantly increased.The data suggested that CDCA could promote hepatic anti-inflammatory responses mediated by M2-type KCs in FLHS layers through acting on JAK-STAT pathway and related regulatory factors.The present study indicated that CDCA could alleviate hepatic inflammation response in FLHS laying hens by improving antioxidant and autophagy abilities,inhibiting the inflammatory response mediated by M1-type KCs polarization,and promoting the anti-inflammatory response mediated by M2-type KCs polarization.