Experimental Study On The Functional Alteration Of Hyperplastic Brown Adipose Tissue Under High-fat-diet Due To Over-expression Of Ap2-SREBP-1C

ObjectiveAdipose tissue is one of the major target organs of insulin,and plays a key role in the pathology of insulin resistance(IR).Adipose tissue dysfunction cause glucose and lipid metabolic disorders,leading to a series of metabolic diseases.Both obesity and lipodystrophy can result in Adipose tissue dysfunction.Brown adipose tissue are rich in mitochondria,on which UCPs induce thermogenesis dependent.Thus BAT is crucial in energy metabolism and has caused extensive concern.In order to deeply explore the role of lipodystrophy in insulin resistance,we intend to investigate the metabolic characteristics of ap2-SREBP-1C transgenic mice,what’s more,we also observe the changes of BAT function under HFD.Methods1,8 weeks old ap2-SREBP-1C transgenic mice and its littermates were i ncluded,food intake,body weight was measured while blood glucose and p lasma TG,TC,LDL-C,Glucose were determined.Insulin sensitivity was eval uated by an oral glucose tolerance test(OGTT)and HOMA-IR.Leptin was de termined,too.After execution,weigh of liver,adipose tissue were calcu lated and sent for HE and ORO staining,hepatic and muscular lipid content were determined.BAT function marker UCP-1 were determined by PCR.2、ap2-SREBP-1C transgenic mice and its littermates were randomly divided into 4 groups:WT,WT+HFD,TG,TG+HFD,each for 9.The high fat diet consist of 4%protein,41.0%carbohydrate,24.0%fat.During the experimental session,the parameters above were repeated,in the same time,adipose transcription regulatory factor(PRDM16),cytochrome C oxidase subunit 8a(Cox8a)was also detected by RT-PCR.Results1,Compared to their wild type littermates,each part(perirenal fat,perigonal fat,subcutaneous fat)of WAT of Tg mice were atrophy(P<0.01),whereas subscapular brown adipose tissue was significantly hypertrophic(P<0.01).HE staining shows that BAT presents an abnormal light colored,uneven-size and biggish lipid droplets.mRNA expression of BAT function marker UCP-1 is much decreased(P<0.01).2,Liver gained much more in transgenic mice than its littermates(P<0.01),biopsy showed significantly pathological changes of fatty liver,and TG content in liver increase significantly(P<0.05).3,Plasma insulin,glucose and HOMA-IR raised significantly(P<0.05),plasma TG shows no noteworthy variation,while fasting plasma TC and LDL-C were higher(P<0.05,P<0.01).4,Leptin level decreased significantly(P<0.01).5,High-fat-diet does not change the curve of OGTT and fasting glucose effectively(P>0.01).6,High-fat-diet has a reduced effect on wilt-type 7,HFD can increase the cell amount of WAT(visceral and subcutaneous)in wild-type mice(P<0.05),but has no effect on transgenic mice(P>0.05).In the same time,it can’t promote the amount of BAT in wild-type(P>0.05),but can significantly decrease the amount of BAT in transgenic mice(P<0.05).8.HFD can decrease the UCP-1 mRNA expression(P<0.05),also the PRDM16 and Cox8a gene expression(P<0.05).Conclusions1,aP2-SREBP-1c transgenic mice exists significant abnormal morphology and dysfunction of adipose tissue.Also,it’s an advisable model for glucose-lipid metabolic disorder diseases such as fatty liver,hypercholesteremia,and type 2 diabetes.2,High-fat-diet induces degeneration of BAT by exhibiting brown adipogenesis and promote the apoptosis of mitochondrial,which is closely related to overexpression of SREBP-1C in adipose tissue.