Exploring The Mechanism Between TNF-α And Wnt/β-catenin Signaling Pathway During The Differentiation Process Of Mouse Primary Preadipocytes

Obesity is mainly due to the recruitment, proliferation and differentiation of preadipocytes,Obese patients are increasing year by year, and now it has become an important disease thatthreat to human health. Obesity can not olny cause diabetes, atherosclerosis hypertension ele-vate blood lipids and some related diseases, but also can cause asthma, breast cancer and fat-ty liver. In recent years, with the significant rise of obesity rates, has caused widespread cone-cern.TNF-α was considered as an inflammatory factor that plays roles in immune response, Inrecent years it become a new adipokines, obesity has also been identified as an inflammation.Activation of Wnt/β-catenin signaling pathway can inhibit the differentiation of preadipocy-tes.However in the process of obesity, especially during the formation of adipocytes,the roleof it is still unclear. There are some crosstalks between TNF-α and Wnt/β-catenin signalingpathway, affecting the differentiation of preadipocytes. In this article, we studied the the keymolecule of β-catenin which is impacted by TNF-α in the Wnt/β-catenin signaling pathway,the protein of PPARγ and adiponectin are changed during inducing, in order to describe theinteraction of TNF-α and Wnt/β-catenin signaling pathway during the differentiation of mo-se primary preadipocytes. The experimental results shown:①Mouse primary preadipocytes was isolated by collagenase digestion, and then cultured, tobuild the primary mouse preadipocytes model.②Mouse primary preadipocytes were induced by three ways, and the best way was selectedsuccessfully.The final adipogenic differentiation rate is80%, and laid the cellular basis forthe following experiments③100ng/mLTNF-α was added In vitro, it can extremely inhibit the differentiation of pre-adipocytes (p <0.01), maintains undifferentiated state, and reduces the induction rate, th- erefore our experiments used100ng/mL TNF-α. We uccessfully established TNF-α overexpression and deletion model, it laid the foundation of studying the relationship betweenTNF-α and Wnt/β-catenin signaling pathway. Morphological observation, the addition ofTNF-α to cells maintains them an undifferen-tiated state, inhibits the differ-entiation ofpreadipocytes, after inducing for14days the number of adipocytes was significantly low-er than WT (p <0.01); the number of adipocytes of TNF-α deletion mice in the ind-uctionrate increased significantly (p <0.05), on day14induction of TNF-α can suppress thedifferentiation of preadipocytes.④At the molecular level, β-catenin mRNAand protein expression are declined during celldifferentiation, the protein level of PPARγ and adiponectin are upregulated, while the ad-dition of TNF-α and expression levels are increased significantly (p <0.05), and for theaddition of TNF-α adipogenicrelated protein expression declined down extremely signifi-cantly (p <0.01). It proves that TNF-α can maintain β-catenin from degradation, therebyactivate the Wnt/of β-catenin signal pathway, reduce the generation of lipid-associatedprotein, inhibit of the differentiation of preadipocytes.