Effect Of Toll-like Receptor 2 On Adipose Tissue Fibrosis Of Obese Mice And Its Mechanism

ObjectTo investigate the effect of toll-like receptor 2 on adipose tissue fibrosis of obese mice and its mechanism.MethodsHealthy C57BL/6J mice and toll-like receptor 2 gene knocking out mice were hybridized to obtain TLR2^{wild type} and TLR2^deficiency mice were given common chow or high fat diet.After feeding for 16weeks,epididymal adipose tissue were collected for further research.Paraffin section were used to observe adipocytes size and morphology by hematoxylin-eosin staining.To demonstrate the collagen deposition in adipose tissue,Masson staining was carrying out.Collagen 1,collagen6,toll-like receptor 2,myeloid differentiation protein 88,p38mitogen-activated protein kinase,phosphorylated p38 mitogen-activated protein kinase,interleukin 6,tumor necrosis factor?,matrix metalloproteinase 1,tissue inhibitor of matrix metalloproteinase 1,interleukin 29 and F4/80 protein expression and?or?mRNA levels were measured by western blotting and?or?fluorescence real-time quantitative PRC or immunohistochemistry.Raw 264.7cell line and primary macrophages were cultured in the medium with free fatty acid and?or?interleukin 29 or without free fatty acid and?or?interleukin 29before harvested.Toll-like receptor 2 of Raw 264.7 cell line were detected by immunofluorescence.Myeloid differentiation protein 88 expression levels were measured by western blotting.Interleukin 6 and tumor necrosis factor?mRNA were observed by fluorescence real-time quantitative PCR.Tissue inhibitor of matrix metalloproteinase 1 levels in the medium were measured by ELISA.ResultsAnimal experiments results were showed as followings.Compared with TLR2^{wild type} mice with normal chow,total collagen,collagen 1,collagen 6,interleukin 29,toll-like receptor 2,myeloid differentiation protein 88,p38mitogen-activated protein kinase,phosphorylated p38 mitogen-activated protein kinase,interleukin 6 mRNA,tumor necrosis factor?mRNA,tissue inhibitor of matrix metalloproteinase 1 increased,while matrix metalloproteinase 1decreased in the adipose tissue of TLR2^{wild type} mice with high-fat diet.Compared with TLR2^{wild type} mice with high fat diet,total collagen,collagen 1,collagen 6,interleukin 29,toll-like receptor 2,myeloid differentiation protein 88,p38 mitogen-activated protein kinase,phosphorylated p38 mitogen-activated protein kinase,interleukin 6 m RNA,tumor necrosis factor?mRNA,tissue inhibitorofmatrixmetalloproteinase1decreased,whilematrix metalloproteinase 1 increased in the adipose tissue of TLR2^deficiency mice with high fat diet.Cell experiments results were showed as following.IL-29 and FFA activated Raw264.7 cell expression synergistically.TLR2 antibody or TLR2gene knocking out could blocking the effect.ConclusionToll-like receptor 2 mediates fibrosis in adipose tissue of high fat diet?induced obese mice via tissue inhibitor of matrix metalloproteinase 1.