The Effects Of Decreased BMP9 Expression Level On Metabolism Of Mice

Objective:To investigate the effects of decreased BMP9 expression level on glucose and lipid metabolism in mice.Methods:95 male C57BL/6J mice were randomly divided into normal chow diet group（ND）and high fat diet group（HFD）.All mice were injected with Polymeric core-shell nanoparticle（PCNs）,shBMP9 and PCNs/shBMP9 via tail vein,and divided into ND-PCNs group（N-PCNsgroup,n=5）,ND-shBMP9group（N-shBMP9group,n=5）,ND-PCNs/shBMP9 group（N-PCNs/shBMP9 group,n=5）,HFD-PCNs group（H-PCNs group,n=5）,HFD-shBMP9 group（H-shBMP9 group,n=5）and HFD-PCNs/shBMP9group（H-PCNs/shBMP9 group,n=5）at the 16^thweek.The variation of body weight,food intake,fasting glucose（FBG）,fed blood glucose,fasting insulin（FIns）,total cholesterol（TC）,triglyceride（TG）and free fatty acid（FFA）were detected.Intraperitoneal glucose tolerance test（GTT）,inulin tolerance test（ITT）and hyperinsulinemic-euglycemic clam technique were carried out to evaluated glucose-lipid metabolism and insulin sensitivity.The expression level of Bone morphogenetic protein 9（BMP9）mRNA and protein in liver were measured by realtime fluorescence quantitative（RT-PCR）and Western blot.Results:After high fat diets for 16 weeks,the body weight,FBG,FIns,TC,TG and FFA in HFD group were significantly increased compared with ND group（P<0.05 or 0.01）.There were no significant differences between N-shBMP9 group and N-PCNs/shBMP9 group in body weight,food intake,FBG,fed blood glucose,FIns,TC,TG and FFA（P>0.05）,there were no significant differences between H-shBMP9 group and H-PCNs/shBMP9 group in body weight and food intake（P>0.05）,the FBG,fed blood glucose,FIns,TC,TG and FFA in H-PCNs/shBMP9 group were significantly increased compared with H-shBMP9 group（P<0.05 or 0.01）.The level of BMP9 mRNA and protein in H-PCNs/shBMP9 group were significantly decreased compared with H-shBMP9 group（P<0.01）.There were no significant differences between N-shBMP9 group and N-PCNs/shBMP9 group in the area under curve during GTT and ITT（P>0.05）,the area under curve during GTT and ITT in H-PCNs/shBMP9 group were significantly increased compared with H-shBMP9 group（P<0.05 or 0.01）.During the steady-state of clamp,N-PCNs/shBMP9 group had no significant differences in Glucose infusion rate（GIR）,Glucose disappearance rate（GRd）,Hepatic glucose production（HGP）,HGP suppression,TC,TG and FFA compared with N-shBMP9 group（P>0.05）,the GIR,GRd and HGP suppression in H-PCNs/shBMP9group were significantly decreased compared with H-shBMP9 group（P<0.05 or 0.01）,while HGP,TC,TG and FFA were significantly increased compared with H-shBMP9group（P<0.01）.Conclusion:Deacreased BMP9 expression level in liver can aggravate insulin resistance,glucose and lipid metabolism disorders in HFD mice.