Study On The Effect Of Lipodystrophy And Obesity On The Anti-lipolysis Of Insulin

Objective:This research use the fat metabolism disorder of transgenic mice and leptin deficiency type obese mice as the research object,explore the adipose tissue in different pathological state(hypertrophy/ lipodystrophy)of lipid levels,insulin to find corresponding to the change of lipid regulation and control of solution under the condition of the key factor of the influence of adipose tissue insulin function,find related influence mechanism,thus providing basis for glucolipid metabolic disease theory research.Methods: Lipodystrophy mice(a P2-SREBP1c)and obese mice(ob/ob)were fed to the age of 16 weeks.Determine the fat content and determine the fat distribution;The pathological features of subcutaneous adipose tissue and brown adipose tissue were observed by pathological staining.The expression of lipolysis and its related pathway genes in mouse adipose tissue was detected.TGFβ receptor inhibitor interfered with the two models in vivo to observe and compare the changes in metabolic characterization,adipose tissue morphology,transcription levels and protein levels of insulin pathway and lipolysis related genes.Adipogenic differentiation induced by 3T3-L1 preadipocytes at the cellular level verified the effect of inhibition of TGFβ pathway conduction in normal adipocyte morphology on insulin pathway expression and lipid gene expression.Results: 1.a P2-SREBP1 c transgenic mice had dysplasia of white fat,lipid heterotopic deposition in the liver and brown fat,and the brown fat became white.The mice had obvious glycolipid metabolic disorder and insulin resistance phenotype,hyperexpression of TGFβ pathway in subcutaneous adipose tissue,and expression of insulin pathway and lipolysis related genes was inhibited.2.Ob/ob mice obese white fat hypertrophy,ectopic lipid deposition,brown adipose tissue,clear white mice sugar lipid disorder traits such as hyperglycemia,hyperlipidemia,insulin resistance,hypodermic and adipose tissue TGFβ access high expression of insulin receptor expression is suppressed,insulin receptor pathways downstream of genes involved in stress and lipid solutions for high expression.3.AP2-SREBP1 c transgenic mice and ob/ob obese mice were two opposite models of adipose tissue morphological and pathological changes,but they both showed high expression of TGFβ pathway as well as changes in insulin pathway expression and impaired function.4.TGFβ receptor inhibitor in vivo intervention of a P2-SREBP1 c transgenic mice,mice glucose and lipid metabolism disorder improved,white fat tissue quality increased,brown fat white degree improved,insulin pathway conduction increased,insulin sensitivity significantly improved.5.TGFβ receptor inhibitor in vivo interfered with ob/ob obese mice,and the insulin pathway conduction of the mice increased,but the metabolic phenotype changes were not obvious.Conclusion: 1.AP2-SREBP1 c mice and ob/ob mice showed decreased glucose tolerance and impaired insulin function,although adipose tissue morphology was different.TGFβ pathway up-regulated and insulin pathway changed in subcutaneous adipose tissue of the two models,indicating that high expression of TGFβ in adipose tissue would affect the normal performance of insulin function.2.Inhibition of TGFβ pathway can partially improve lipid metabolism in a P2-SREBP1 c mice and ob/ob mice.3.Inhibition of TGFβ pathway can improve fat differentiation in a P2-SREBP1 c mice.4.Inhibition of TGFβ pathway can improve the expression of insulin pathway in a P2-SREBP1 c mice and ob/ob mice,which is achieved by stimulating the phosphorylation of Akt.5.The different changes in insulin pathway expression in aP2-SREBP1 c and ob/ob mice after TGFβ inhibition indicated that the effects of TGFβ signaling intervention on insulin pathway and its function were conditional and influenced by changes in adipose tissue microenvironment.In the case of abnormally differentiated adipocytes(obesity or lipodystrophy),the effect of TGFβ pathway on insulin signaling predated the effect on insulin resistance by restoring overall insulin function.In well-differentiated,functioning cells,the direct regulation of insulin anti-lipolysis by intervention in the TGFβ pathway was directly observed.