Effect Of Nur77 On The Expression Of Brown Adipose Tissue Markers

Objective: Obesity has done a serious threat to human health all over the world,which is closely related to metabolic diseases such as diabetes cardiovascular disease and hypertension.Obesity is caused by a large amount of white fat accumulation;whose main function is to store fat and often associated with inflammation.However,there is another fat tissue,brown adipose tissue,attracting increasing attention,maybe becoming the key to fight obesity.Brown fat contains large amount of mitochondria,which is helpful to produce heat,consuming obesity.Moreover,It has been reported that Nur77,a kind of transcript factor,highly expressed in brown adipocytes,which suggests their closed relationship between them.In this study Nur77-knockout mice were used to research the effect of Nur77 on brown fat and its proportion to white fat.In this process,UCP1(Uncoupling protein)is used as the crucial detected protein associated with brown fat.This study will provide a profound theoretical basis of therapy of obesity.Methods: Four-month-old Nur77-/-mice and wild-type mice were selected.Three males and three females were used in each group.Normal feed diet was used after weaning to extract brown adipose tissue from mouse scapular region.After weighing mice were observed.Morphological changes in brown fat expression of brown adipose tissue marker protein levels;microarray analysis of mouse brown adipose tissue.Results: 1.Successful selection of Nur77 knockout homozygous mice(Nur77-/-).2.In male mice there was no significant difference between the weight of brown adipose tissue and the total weight ratio of Nur77-/-compared with wild type(P>0.05);in female mice Nur77-/-was compared with wild type.The ratio of weight to total weight of brown adipose tissue increased(P<0.01).3.HE staining observed that in male mice Nur77-/-compared with the wild type the number of brown adipose tissue cells decreased fat vacuoles increased cytoplasm content decreased;in female mice Nur77-/-Compared with the wild type brown adipose tissue cells increased fat vacuoles decreased and cytoplasm content increased.4.In male mice the expression of UCP1 protein was lower in Nur77-/-brown adipose tissue than in wild type(P<0.05).In female mice the expression of UCP1 protein in Nur77-/-brown adipose tissue was observed.Significantly higher than wild type(P<0.05).5.Gene chip results suggest that the FBJ osteosarcoma oncogene(Fos)heat shock protein family A(70)member 1A(Hspa1a)and heat shock protein family A(70)member 1B(Hspa1b)heat shock protein 90 A family B member 1(Hsp90ab1)and nitric oxide synthase 3(Nos3)RNA levels were elevated after Nur77 knockout in the estrogen signaling pathway.Conclusion: Nur77 is involved in the expression of brown adipose tissue.In different genders mice,the Nur77 showed gender differences of the expression in brown adipose tissue markers and this differential change may be related to the estrogen conduction pathway.