The Influence Of Tumor Necrosis Factor-alpha For The Chemerin/CMKLR1 Signaling Pathway In Adipocyte

Obesity, characterized by an excess of adipose tissue. Adipose tissue secretes a number ofhormone-like compounds, termed adipokines, that are important for the maintenance of normalglucose metabolism, serum levels of the novel adipokine chemerin are significantly elevatedinmousemodels of obesity/diabetes. The expression of chemerin and itsreceptors,chemokine-like receptor1 are altered in white adipose,skeletal muscle, and liver tissue ofobese/diabetic mice. Chronic low-grade inflammation that occurs in obesity promotes chemerinproduction by adipocytes. Consistent with this, Tumor necrosis factorα（ tumor necrosis factor,TNF-α） treatment of 3T3-L1 adipocytes increased bioactive chemerin levels in the cell media asdetected using a CMKLR1 cell-based bioassay. TNF-αmay enhance prochemerin synthesis andsecretion from adipocytes.TNF-αis a kind of inflammatory markers, a study showed that TNF-αto the occurrence ofobesity has a very important role in fat cells express. Chemerin/CMKLR1 signal pathway is thenew found with fat cell differentiation, activate the Chemerin signaling pathways, can promoteadipose cell differentiation. In the present study Lepr^db/dbmice, Lepr^db/db/TNF-α^-/-double genesmice, TNF-α^-/-mice and WT mice for experimental model, through the Real-time PCR andimmune imprinting technology, detection of mice in 3 weeks and 6 weeks fat tissue of thefactors related to express, this paper discusses TNF-αand chemerin/CMKLR1 signalingpathways of the relationship. The experimental results showed as follows:Weight data show that Lepr^db/db/TNF-α^-/-double genes mice heaviest, Lepr^db/dbmice is thesecond smallest, and TNF-α^-/-mice third, WT mice most light. That TNF-αdeficiency inducesthe mice gain weight and adipose cell differentiation increased. In general that TNF-αdeficiency promotes cell differentiation.Real-time PCR detection chemerin/CMKLR1 signaling pathways related factor expression,the results showed that TNF-αdeficiency, chemerin, C/EBPβ, adiponectin, PPARγ2 andC/EBPαexpression level up; Wnt andβ-catenin expression level of decline. Speculation lack of TNF-αinhibit Wnt andβ-catenin target genes expression, make Wnt andβ-catenin mRNAexpression decline; And then lifted the Wnt to C/EBPαinhibition and make C/EBPαexpressionlevel raised; chemerin upstream gene C/EBPαexpress rises, and thus activatechemerin/CMKLR1 signal pathway, the chemerin mRNA level rises. Chemerin and CMKLR1binding together that lead to ERK1/2 phosphorylation, the phosphorylated ERK1/2 can beinduced to expression of the fat gene expression and adipose cell differentiation.Immune imprinting detectionβ-catenin, C/EBPβ, PPARγ2 and adiponectin protein resultsshow that TNF-αmissing,β-catenin expression decline. This shows that the lack of mice leptinreceptor itself exists a protection mechanism, can restrain obesity. C/EBPβprotein expressionin the TNF-αmissing raised, C/EBPβis C/EBPαthe intimacy competency scale the upstreamWnt gene inhibit C/EBPβto C/EBPα, lead to C/EBPαexpression down. On the one hand, raiseC/EBPαexpression level, on the other hand lift Wnt to C/EBPαinhibition. The C/EBPαactivates Chemerin/CMKLR1 signaling pathways, promotes adipose cell differentiation.PPARγ2 and adiponectin gene is adipose cell differentiation of the symbol of genes that TNF-αmissing, protein expression level raised and promote differentiation.The results show that, the lack of TNF-αpromoted the differentiation of the fat cells, activatethe chemerin/CMKLR1 signal pathways. Speculated that TNF-αmissing suppress Wnt andβ-catenin target genes expression, and then remove the Wnt to C/EBPαinhibition. TheChemerin upstream gene C/EBPαactivates the Chemerin/CMKLR1 signaling pathways, makefat cell differentiation.