Background The role of bile acids in modulating the gut microbiota and their impact on host metabolism has garnered significant attention.Taurochenodeoxycholic acid(TCDCA)is the predominant bile acid within the chicke...Background The role of bile acids in modulating the gut microbiota and their impact on host metabolism has garnered significant attention.Taurochenodeoxycholic acid(TCDCA)is the predominant bile acid within the chicken bile acid pool and is closely related to metabolic disorders.The current study aims to investigate the potential effects of TCDCA on abdominal fat deposition in broilers.From 14 to 28 days of age,the broilers in the CON group received an oral administration of 1 mL of saline,while those in the treatment groups were administered 1 mL of a solution containing 0.05 g,0.10 g,or 0.20 g of TCDCA.Results The results showed that TCDCA treatments from 14 to 28 d had no significant effects on BW,ADFI,ADG and FCR in broilers at the age of 28 days of age.However,the abdominal fat percentage in the 0.20 g TCDCA group significantly increased,accompanied by higher TBA and HDL-c levels,as well as a reduction in apolipoprotein B levels in serum.In addition,serum triglyceride levels tended to be higher in the 0.20 g TCDCA group(P=0.098).The 0.20 g TCDCA treatment increased the gene expressions of SREBP-1,C/EBP-α,and ELOVL6,while decreasing the mRNA abundance of ATGL and CPT-1 in the abdominal fat.Serum levels of TCDCA,TDCA,and THDCA were significantly higher after 0.20 g TCDCA administration,while TCA levels were significantly lower,as determined by the targeted bile acid metabolomics analysis.Conversely,hepatic mRNA levels of CYP7A1,CYP27A1,BAAT,and BSEP were increased in the 0.20 g TCDCA group.The oral administration of 0.20 g TCDCA also upregulated the expression of FXR,VDR,and FGF19 in abdominal fat.The 16S rRNA analysis of cecal microbiota revealed that a decrease in the Shannon and Simpson indexes in the 0.20 g TCDCA group,and an increase in the Firmicutes/Bacteroidetes ratio.LEfSe analysis revealed that the predominant bacteria in the CON group were Streptococcus and Oscillospira at the genus level,while Lactobacillus,Parabacteroides,Anaeroplasma,and Helicobacter were identified as the dominant genera in the 0.20 g TCDCA group.Functional predictions for the gut microbiota exhibited that lipid metabolism,replication and repair pathway were enhanced in the 0.20 g TCDCA group.Correlation analysis demonstrated that the abundance of Lactobacillus was positively correlated with serum levels of TCDCA,THDCA,and TDCA,while the abundance of Streptococcus and Oscillospira showed a positive correlation with serum TCA levels.Conclusion Overall,this study elucidates that the intervention of 0.20 g TCDCA may promote abdominal fat deposition by activating bile acid receptors in abdominal fat,and concurrent alterations in both the intestinal microbial community and bile acid profile.展开更多
Taurochenodeoxycholic acid(TCDCA)is one of the main effective components of bile acid,playing critical roles in apoptosis and immune responses through the TGR5 receptor.In this study,we reveal the interaction between ...Taurochenodeoxycholic acid(TCDCA)is one of the main effective components of bile acid,playing critical roles in apoptosis and immune responses through the TGR5 receptor.In this study,we reveal the interaction between TCDCA and TGR5 receptor in TGR5-knockdown H1299 cells and the regulation of inflammation via the cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)-cAMP response element binding(CREB)signal pathway in NR8383 macrophages.In TGR5-knockdown H1299 cells,TCDCA significantly activated cAMP level via TGR5 receptor,indicating TCDCA can bind to TGR5;in NR8383 macrophages TCDCA increased cAMP content compared to treatment with the adenylate cyclase(AC)inhibitor SQ22536.Moreover,activated cAMP can significantly enhance gene expression and protein levels of its downstream proteins PKA and CREB compared with groups of inhibitors.Additionally,TCDCA decreased tumour necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,IL-8 and IL-12 through nuclear factor kappa light chain enhancer of activated B cells(NF-κB)activity.PKA and CREB are primary regulators of anti-inflammatory and immune response.Our results thus demonstrate TCDCA plays an essential anti-inflammatory role via the signaling pathway of cAMP-PKA-CREB induced by TGR5 receptor.展开更多
基金funded by the National Key Research&Development Program of China(2023YFD1301400 and 2023YFF1001900)the Program for Shaanxi Science&Technology(2022GD-TSLD-46-0302,2023KXJ-243,2023GXJS-02-01 and L2022-QCYZX-NY-004)。
文摘Background The role of bile acids in modulating the gut microbiota and their impact on host metabolism has garnered significant attention.Taurochenodeoxycholic acid(TCDCA)is the predominant bile acid within the chicken bile acid pool and is closely related to metabolic disorders.The current study aims to investigate the potential effects of TCDCA on abdominal fat deposition in broilers.From 14 to 28 days of age,the broilers in the CON group received an oral administration of 1 mL of saline,while those in the treatment groups were administered 1 mL of a solution containing 0.05 g,0.10 g,or 0.20 g of TCDCA.Results The results showed that TCDCA treatments from 14 to 28 d had no significant effects on BW,ADFI,ADG and FCR in broilers at the age of 28 days of age.However,the abdominal fat percentage in the 0.20 g TCDCA group significantly increased,accompanied by higher TBA and HDL-c levels,as well as a reduction in apolipoprotein B levels in serum.In addition,serum triglyceride levels tended to be higher in the 0.20 g TCDCA group(P=0.098).The 0.20 g TCDCA treatment increased the gene expressions of SREBP-1,C/EBP-α,and ELOVL6,while decreasing the mRNA abundance of ATGL and CPT-1 in the abdominal fat.Serum levels of TCDCA,TDCA,and THDCA were significantly higher after 0.20 g TCDCA administration,while TCA levels were significantly lower,as determined by the targeted bile acid metabolomics analysis.Conversely,hepatic mRNA levels of CYP7A1,CYP27A1,BAAT,and BSEP were increased in the 0.20 g TCDCA group.The oral administration of 0.20 g TCDCA also upregulated the expression of FXR,VDR,and FGF19 in abdominal fat.The 16S rRNA analysis of cecal microbiota revealed that a decrease in the Shannon and Simpson indexes in the 0.20 g TCDCA group,and an increase in the Firmicutes/Bacteroidetes ratio.LEfSe analysis revealed that the predominant bacteria in the CON group were Streptococcus and Oscillospira at the genus level,while Lactobacillus,Parabacteroides,Anaeroplasma,and Helicobacter were identified as the dominant genera in the 0.20 g TCDCA group.Functional predictions for the gut microbiota exhibited that lipid metabolism,replication and repair pathway were enhanced in the 0.20 g TCDCA group.Correlation analysis demonstrated that the abundance of Lactobacillus was positively correlated with serum levels of TCDCA,THDCA,and TDCA,while the abundance of Streptococcus and Oscillospira showed a positive correlation with serum TCA levels.Conclusion Overall,this study elucidates that the intervention of 0.20 g TCDCA may promote abdominal fat deposition by activating bile acid receptors in abdominal fat,and concurrent alterations in both the intestinal microbial community and bile acid profile.
基金supported by the National Natural Science Foundation of China(No.31160518)the Key Laboratory of Clinical Diagnosis and Treatment Techniques for Animal Disease(No.B20161012919)。
文摘Taurochenodeoxycholic acid(TCDCA)is one of the main effective components of bile acid,playing critical roles in apoptosis and immune responses through the TGR5 receptor.In this study,we reveal the interaction between TCDCA and TGR5 receptor in TGR5-knockdown H1299 cells and the regulation of inflammation via the cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)-cAMP response element binding(CREB)signal pathway in NR8383 macrophages.In TGR5-knockdown H1299 cells,TCDCA significantly activated cAMP level via TGR5 receptor,indicating TCDCA can bind to TGR5;in NR8383 macrophages TCDCA increased cAMP content compared to treatment with the adenylate cyclase(AC)inhibitor SQ22536.Moreover,activated cAMP can significantly enhance gene expression and protein levels of its downstream proteins PKA and CREB compared with groups of inhibitors.Additionally,TCDCA decreased tumour necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6,IL-8 and IL-12 through nuclear factor kappa light chain enhancer of activated B cells(NF-κB)activity.PKA and CREB are primary regulators of anti-inflammatory and immune response.Our results thus demonstrate TCDCA plays an essential anti-inflammatory role via the signaling pathway of cAMP-PKA-CREB induced by TGR5 receptor.
