Research Of The Molecular Mechanism For The Glucose-Lipid Metabolism Change In TNF-Alpha Induced Insulin Resistant Mice

Objective: To investigate the effects and the molecular mechanism of TNF-αinduced insulin resistance on the related genes of glucose-lipid metabolism in mice.Methods: Male C57BL/6J mice were randomly divided into 2 groups. The mice were given an intraperitoneal injection of TNF-α(TNF group , 6μg/kg/d ;n=10) and saline (NC group, n=10) for 7 days. After 7 days, we analyzed the in vivo role of TNF-αon some metabolism-related genes and adipocytokines in the development of insulin resistance.Results: 1) TNF-αtreament resulted in a marked increasing fasting blood glucose, insulin, free fatty acids (FFA) compared with NC group ( p< 0.01 and p < 0.05 seperately ), and a slightly increasing TG,TC compared with NC group (p >0 .05 ); 2) The adipocyte ADPN mRNA expression in adipose tissues and ADPN protein in plasma were decreased ( p< 0.01) ; visfatin mRNA expression in adipose tissues and visfatin protein in plasma were decreased ( p < 0.05 and p <0.01 seperately ) and FGF-21 mRNA expression in liver tissues was not significantly changed ( p> 0.05 ) ; 3) The ATGL mRNA expression and ATGL protein in adipose tissues were decreased (p<0.01 and p<0.05 seperately); HSL mRNA in adipose tissues and CPT-1 mRNA in liver tissues were not significantly changed(p>0.05). 4) The mRNA expression of SREBP-2 ,HMGCR,LDLR mRNA in liver tissues were not significantly changed(p>0.05). 5) The PPARγmRNA expression in adipose tissues were significantly decreased(P<0.05); the PPARδmRNA expression in liver tissues were significantly decreased(P<0.05); the PPARγand PPARαmRNA expression in liver tissues was not significantly changed(P>0.05). 6) In adipose tissues, PPARγand ADPN mRNA expression were significantly positively related(p<0.01), PPARγand ATGL mRNA expression were significantly positively related(p<0.05).Conclusion: TNFαdownregulates some glucose-lipid metabolism related genes such as ADPN,visfatin,ATGL in adipose and some PPARs family genes such as PPARγin adipose and PPARδin liver;the downregulation effects to ADPN and ATGL transcription might be through PPARγpathways. TNFαhad small influences to cholesterol metabolism related genes such as HMGCR,SREBP-2,LDLR in liver tissues.