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.