Beneficial effect of Xinjiang composite probiotics from camel milk on lipid metabolism in db/db mice via modulating bile acids
The aim of this study was to investigate the modulatory effects of composite probiotics from camel milk(CPCM)on blood lipids and their mechanisms from the perspective of bile acids metabolism.32 db/db diabetic mice were divided into a model group,a positive drug group,a composite probiotics low and high dose group,and 8 db/m mice as a normal control group.The basic biochemical indexes related to blood glucose and blood lipids were detected,and liver tissue sections were made for analysis;changes in bile acids profiles were detected by liquid chromatogra-phy-mass spectrometry hyphenation(LC-MS),and chol esterol metabolism-related genes and protein expression were detected by Real-time PCR and protein immunoblotting.CPCM significantly reduced serum levels of glycosylated haemoglobin,total cholesterol,triglycerides and LDL cholesterol,decreased hepatic steatosis,and reduced the number and volume of intracellular lipid vacuoles in hepatocytes in db/db mice.After the CPCM intervention,total bile acids(TBA)in serum decreased,TBA in faeces increased,the ratio of primary bile acids(PBA)to secondary bile acids(SBA)in both serum and faeces decreased;the percentage of free bile acids in serum increased,and the percentage of bound bile acids in faeces increased;the levels of farnesol X receptor(FXR)and agonists of Takeda G protein-coupled receptor 5(TGR5),Lithocholic acid(LCA)and Chen-odeoxycholic acid(CDCA),in bile acids were increased,and FXR's inhibitors Tauro-α-muricholic acid(T-α-MCA)and Tauro-β-muricholic acid(T-β-MCA)decreased.After the intervention of CPCM,the expression of FXR increased in the liver of mice,the expression of peroxisome prolifer-ator-activated receptor γ(PPARγ)and liver X receptor α(LXRα)significantly increased in the colon,and the expression of cholesterol absorption protein NPC1-like intracellular cholesterol transporter protein 1(NPC1L1)significantly decreased.The composite probiotics improved glycolipid metabolism in db/db mice,improved the compositional structure of bile acids in db/db mice,increased the agonists of FXR and TGR5 in bile acids,LCA and CDCA,decreased the inhibitors of FXR in bile acids,T-α-MCA and T-β-MCA,and promoted the expression of FXR as well as TGR5,and regulated the lipid metabolism of the liver in mice.CPCM may inhibit intestinal cholesterol absorption and regulate lipid metabolism in db/db mice through the PPARγ-LXRα-NPC1L1 pathway.
composite probiotics from camel milk(CPCM)type 2 diabetesbile acidslipid metabolismcholesterolNPC1L1
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