Background Ginkgo biloba extract(GBE)is evidenced to be effective in the prevention and alleviation of metabolic disorders,including obesity,diabetes and fatty liver disease.However,the role of GBE in alleviating fatt...Background Ginkgo biloba extract(GBE)is evidenced to be effective in the prevention and alleviation of metabolic disorders,including obesity,diabetes and fatty liver disease.However,the role of GBE in alleviating fatty liver hemorrhagic syndrome(FLHS)in laying hens and the underlying mechanisms remain to be elucidated.Here,we investigated the effects of GBE on relieving FLHS with an emphasis on the modulatory role of GBE in chicken gut microbiota.Results The results showed that GBE treatment ameliorated biochemical blood indicators in high-fat diet(HFD)-induced FLHS laying hen model by decreasing the levels of TG,TC,ALT and ALP.The lipid accumulation and pathological score of liver were also relieved after GBE treatment.Moreover,GBE treatment enhanced the antioxidant activity of liver and serum by increasing GSH,SOD,T-AOC,GSH-PX and reducing MDA,and downregulated the expression of genes related to lipid synthesis(FAS,LXRα,GPAT1,PPARγand Ch REBP1)and inflammatory cytokines(TNF-α,IL-6,TLR4 and NF-κB)in the liver.Microbial profiling analysis revealed that GBE treatment reshaped the HFD-perturbed gut microbiota,particularly elevated the abundance of Megasphaera in the cecum.Meanwhile,targeted metabolomic analysis of SCFAs revealed that GBE treatment significantly promoted the production of total SCFAs,acetate and propionate,which were positively correlated with the GBE-enriched gut microbiota.Finally,we confirmed that the GBE-altered gut microbiota was sufficient to alleviate FLHS by fecal microbiota transplantation(FMT).Conclusions We provided evidence that GBE alleviated FLHS in HFD-induced laying hens through reshaping the composition of gut microbiota.Our findings shed light on mechanism underlying the anti-FLHS efficacy of GBE and lay foundations for future use of GBE as additive to prevent and control FLHS in laying hen industry.展开更多
Background Magnolol(MAG)exhibits hepatoprotective activity,however,whether and how MAG regulates the gut microbiota to alleviate fatty liv er hemorrhagic syndrome(FLH S)remains unclear.Therefore,we investigated the me...Background Magnolol(MAG)exhibits hepatoprotective activity,however,whether and how MAG regulates the gut microbiota to alleviate fatty liv er hemorrhagic syndrome(FLH S)remains unclear.Therefore,we investigated the mechanism of MAG in FLHS laying hens with an emphasis on alterations in the gut-liver axis.We randomly divided 54056-week-old Hy-line white laying hens with FLSH into 4 groups.The birds were fed a high-fat low-protein(HFLP)diet(CON).or HELP diets supplemented with 200,400,and 600 mg/kg of MAG(M1,M2,and M3,respectively)for 9 weeks.Results Magnolol supplementation increased the laying rate and ameliorated hepatic damage and dysfunction by regulating lipid metabolism,improving intestinal barrier function,and shaping the gut microbiota and tryptophan metabolic profiles.Dietary MAG supplementation downregulated the expression of lipid synthesis genes and upregulated the expression of lipid transport genes at varying degrees.The intestinal barrier function was improved by 200and 400 mg/kg of MAG supplementation,as evidenced by the increased villus height and mRNA expression of tight junction related genes.Microbiological profile information revealed that MAG changed the gut microbiota,especially by elevating the abundances of Lactobacillus,Faecallbacterium,and Butyricicoccus.Moreover,non-targeted metabolomic analysis showed that MAG significantly promoted tryptophan metabolites,which was positively correlated with the MAG-enriched gut microbiota.The increased tryptophan metabolites could activate aryl hydrocarbon receptor(AhR)and relieved hepatic inflammation and immune response evidenced by the downregulated the gene expression levels of pro-inflammatory cytokines such as interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and inte rleukin-6(IL-6)in the liver.The fecal microbiota transplantation(FMT)experiments further con firmed that the hepatoprotective effect is likely mediated by MAG-altered gut microbiota and their metabolites.Conclusions Magnolol can be an outstanding supplement for the prevention and mitigation of FLHS in laying hens by positively regulating lipid synthesis and transport metabolism,improving the intestinal barrier function,and relieving hepatic nmation by reshaping the gut microbiota and metabolite profiles through gut microbiota-indole metabolite-hepatic AhR crosstalk.These findings elucidate the mechanisms by which MAG alleviates FLHS and provide a promising method for preventing liver diseases by modulating gut microbiota and their metabolites.展开更多
Fibronectins (FNs) are major extracellular proteins in blood plasma and many tissues of vertebrates, and play important roles in adhesion, migration and differentiation of cells. We have identified a novel variant (FN...Fibronectins (FNs) are major extracellular proteins in blood plasma and many tissues of vertebrates, and play important roles in adhesion, migration and differentiation of cells. We have identified a novel variant (FN3) of fibronectin in zebrafish. FN3 mRNA is abundant, as detected by whole-mount in situ hybridization, in the presomitic mesoderm and the newly formed somites, but less abundant in mature somites. Ectopic expression of Sonic Hedgehog (SHH) results in a decrease of FN3 expression, whereas the expression level of FN3 increases in the flhi mutants that lack the notochord. Our results suggest that FN3 may be involved in the formation of somites, but during somite differentiation its expression needs to be downregulated by signals derived from the axial tissues.展开更多
基金funded by the National Key Research and Development Program of China(2022YFA1304201)the Beijing Natural Science Foundation(6222032)+2 种基金the Starting Grants Program for Young Talents at China Agricultural Universitythe 2115 Talent Development Program of China Agricultural UniversityChinese Universities Scientific Fund。
文摘Background Ginkgo biloba extract(GBE)is evidenced to be effective in the prevention and alleviation of metabolic disorders,including obesity,diabetes and fatty liver disease.However,the role of GBE in alleviating fatty liver hemorrhagic syndrome(FLHS)in laying hens and the underlying mechanisms remain to be elucidated.Here,we investigated the effects of GBE on relieving FLHS with an emphasis on the modulatory role of GBE in chicken gut microbiota.Results The results showed that GBE treatment ameliorated biochemical blood indicators in high-fat diet(HFD)-induced FLHS laying hen model by decreasing the levels of TG,TC,ALT and ALP.The lipid accumulation and pathological score of liver were also relieved after GBE treatment.Moreover,GBE treatment enhanced the antioxidant activity of liver and serum by increasing GSH,SOD,T-AOC,GSH-PX and reducing MDA,and downregulated the expression of genes related to lipid synthesis(FAS,LXRα,GPAT1,PPARγand Ch REBP1)and inflammatory cytokines(TNF-α,IL-6,TLR4 and NF-κB)in the liver.Microbial profiling analysis revealed that GBE treatment reshaped the HFD-perturbed gut microbiota,particularly elevated the abundance of Megasphaera in the cecum.Meanwhile,targeted metabolomic analysis of SCFAs revealed that GBE treatment significantly promoted the production of total SCFAs,acetate and propionate,which were positively correlated with the GBE-enriched gut microbiota.Finally,we confirmed that the GBE-altered gut microbiota was sufficient to alleviate FLHS by fecal microbiota transplantation(FMT).Conclusions We provided evidence that GBE alleviated FLHS in HFD-induced laying hens through reshaping the composition of gut microbiota.Our findings shed light on mechanism underlying the anti-FLHS efficacy of GBE and lay foundations for future use of GBE as additive to prevent and control FLHS in laying hen industry.
基金financially supported by the Key Research&Development Program of Zhejiang Province(Grant no:2024C02004)the Collaborative Extension Program for Advancements in Agricultural Technologies of Zhejiang Province(Grant no:2023ZDXT15)。
文摘Background Magnolol(MAG)exhibits hepatoprotective activity,however,whether and how MAG regulates the gut microbiota to alleviate fatty liv er hemorrhagic syndrome(FLH S)remains unclear.Therefore,we investigated the mechanism of MAG in FLHS laying hens with an emphasis on alterations in the gut-liver axis.We randomly divided 54056-week-old Hy-line white laying hens with FLSH into 4 groups.The birds were fed a high-fat low-protein(HFLP)diet(CON).or HELP diets supplemented with 200,400,and 600 mg/kg of MAG(M1,M2,and M3,respectively)for 9 weeks.Results Magnolol supplementation increased the laying rate and ameliorated hepatic damage and dysfunction by regulating lipid metabolism,improving intestinal barrier function,and shaping the gut microbiota and tryptophan metabolic profiles.Dietary MAG supplementation downregulated the expression of lipid synthesis genes and upregulated the expression of lipid transport genes at varying degrees.The intestinal barrier function was improved by 200and 400 mg/kg of MAG supplementation,as evidenced by the increased villus height and mRNA expression of tight junction related genes.Microbiological profile information revealed that MAG changed the gut microbiota,especially by elevating the abundances of Lactobacillus,Faecallbacterium,and Butyricicoccus.Moreover,non-targeted metabolomic analysis showed that MAG significantly promoted tryptophan metabolites,which was positively correlated with the MAG-enriched gut microbiota.The increased tryptophan metabolites could activate aryl hydrocarbon receptor(AhR)and relieved hepatic inflammation and immune response evidenced by the downregulated the gene expression levels of pro-inflammatory cytokines such as interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and inte rleukin-6(IL-6)in the liver.The fecal microbiota transplantation(FMT)experiments further con firmed that the hepatoprotective effect is likely mediated by MAG-altered gut microbiota and their metabolites.Conclusions Magnolol can be an outstanding supplement for the prevention and mitigation of FLHS in laying hens by positively regulating lipid synthesis and transport metabolism,improving the intestinal barrier function,and relieving hepatic nmation by reshaping the gut microbiota and metabolite profiles through gut microbiota-indole metabolite-hepatic AhR crosstalk.These findings elucidate the mechanisms by which MAG alleviates FLHS and provide a promising method for preventing liver diseases by modulating gut microbiota and their metabolites.
基金the National Natural Science Foundation ofChina (Grant Nos. 30025020 and 39970360), TRAPOYT of MOE, and the "863" Program (Grant No. 2001AA221241).
文摘Fibronectins (FNs) are major extracellular proteins in blood plasma and many tissues of vertebrates, and play important roles in adhesion, migration and differentiation of cells. We have identified a novel variant (FN3) of fibronectin in zebrafish. FN3 mRNA is abundant, as detected by whole-mount in situ hybridization, in the presomitic mesoderm and the newly formed somites, but less abundant in mature somites. Ectopic expression of Sonic Hedgehog (SHH) results in a decrease of FN3 expression, whereas the expression level of FN3 increases in the flhi mutants that lack the notochord. Our results suggest that FN3 may be involved in the formation of somites, but during somite differentiation its expression needs to be downregulated by signals derived from the axial tissues.
