GR-mediated transcriptional regulation of m^(6)A metabolic genes contributes to dietinduced fatty liver in hens

Background:Glucocorticoid receptor(GR)mediated corticosterone-induced fatty liver syndrome(FLS)in the chicken by transactivation of Fat mass and obesity associated gene(FTO),leading to demethylation of N6-methyladenosine(m^(6)A)and post-transcriptional activation of lipogenic genes.Nutrition is considered the main cause of FLS in the modern poultry industry.Therefore,this study was aimed to investigate whether GR and m^(6)A modification are involved in high-energy and low protein(HELP)diet-induced FLS in laying hens,and if true,what specific m^(6)A sites of lipogenic genes are modified and how GR mediates m^(6)A-dependent lipogenic gene activation in HELP diet-induced FLS in the chicken.Results:Laying hens fed HELP diet exhibit excess(P<0.05)lipid accumulation and lipogenic genes activation in the liver,which is associated with significantly increased(P<0.05)GR expression that coincided with global m^(6)A demethylation.Concurrently,the m^(6)A demethylase FTO is upregulated(P<0.05),whereas the m^(6)A reader YTHDF2 is downregulated(P<0.05)in the liver of FLS chickens.Further analysis identifies site-specific demethylation(P<0.05)of m^(6)A in the mRNA of lipogenic genes,including FASN,SREBP1 and SCD.Moreover,GR binding to the promoter of FTO gene is highly enriched(P<0.05),while GR binding to the promoter of YTHDF2 gene is diminished(P<0.05).Conclusions:These results implicate a possible role of GR-mediated transcriptional regulation of m^(6)A metabolic genes on m^(6)A-depenent post-transcriptional activation of lipogenic genes and shed new light in the molecular mechanism of FLS etiology in the chicken.

Lactiplantibacillus plantarum FRT4 attenuates high-energy low-protein dietinduced fatty liver hemorrhage syndrome in laying hens through regulating gut-liver axis

Background Fatty liver hemorrhage syndrome(FLHS)becomes one of the most major factors resulting in the laying hen death for caged egg production.This study aimed to investigate the therapeutic effects of Lactiplantibacillus plan-tarum(Lp.plantarum)FRT4 on FLHS model in laying hen with a focus on liver lipid metabolism,and gut microbiota.Results The FLHS model of laying hens was established by feeding a high-energy low-protein(HELP)diet,and the treatment groups were fed a HELP diet supplemented with differential proportions of Lp.plantarum FRT4.The results indicated that Lp.plantarum FRT4 increased laying rate,and reduced the liver lipid accumulation by regulating lipid metabolism(lipid synthesis and transport)and improving the gut microbiota composition.Moreover,Lp.plan-tarum FRT4 regulated the liver glycerophospholipid metabolism.Meanwhile,“gut-liver”axis analysis showed that there was a correlation between gut microbiota and lipid metabolites.Conclusions The results indicated that Lp.plantarum FRT4 improved the laying performance and alleviated FLHS in HELP diet-induced laying hens through regulating“gut-liver”axis.Our findings reveal that glycerophospholipid metabolism could be the underlying mechanism for the anti-FLHS effect of Lp.plantarum FRT4 and for future use of Lp.plantarum FRT4 as an excellent additive for the prevention and mitigation of FLHS in laying hens.

Effect of restricted feeding on hen performance,egg quality and organ characteristics of individual laying hens

This study was to assess the impact of permanent or temporary restricted feeding on laying hen production traits,physiology,and egg quality.Two hundred and forty individually housed ISA Brown hens were monitored across 2 phases,assigned to 3 treatments:ad libitum feeding(ALF),temporary restricted feeding(TRF)and permanent restricted feeding(PRF),n=80 hens per treatment.In Phase 1(P1),22 to40 weeks,the TRF and PRF hens were offered 115 g of feed daily.In Phase 2(P2),41 to 46 weeks,the TRF hens were transitioned to ALF status while the ALF and PRF hens remained as in P1.From 35 to 40 weeks,eggs were collected once weekly from 15 hens per treatment and assessed for differences in albumen,yolk,and shell variables.At 45 weeks,10 hens each from the ALF and PRF groups were euthanized and differences in organ characteristics were assessed.In P1,feed intake,feed to egg conversion ratio and body weight(BW)change were lower(P<0.01),while albumen height and Haugh unit were higher(P<0.01)in both PRF and TRF hen treatments compared to hens allocated the ALF treatment.In P2,TRF and ALF hens had a higher egg production and egg mass than PRF(P<0.01)than ALF.Body weight change in P2 was higher in TRF and similar in both ALF and PRF,while feed intake and feed conversion ratio were higher in TRF followed by ALF and least in the PRF treatment group(P<0.01).At 45 weeks ALF hens had a greater abdominal fat pad weight and fatty liver haemorrhagic syndrome lesion score compared to PRF.Restricting hens to 115 g of feed per day from point of lay restrained BW,improved feed conversion ratio and albumen quality and reduced abdominal fat pad deposition and clinical signs of fatty liver haemorrhagic syndrome in individually housed laying hens.