The Influence Of Hydroxycamptothecine On Mice With Different Genotypes

Nowadays, obesity has become a worldwide health problem with the rapid development ofour society，incorrect components of diet and the irregular life style. What’s more, obesity cannot only cause many negative effects on human’s physical and psychological health, but alsoaffect their work status. As we all know, obesity did seriously damage the living standards ofpeople, so it’s especially important to do studies on obesity and the relative pathologicalmechanisms.Wnt/β-catenin signaling pathway is found to inhibit adipogenesis both in vivo and in vitroresearchs. Tumor necrosis factor-α (TNF-α) can play a similar role to Wnt/β-catenin signalingpathway in adipose tissues, that is, all of them can inhibit the central regular factors PPARγ andC/EBPα. DKK1can block the Wnt signal through uniting the Wnt receptor LRP5and anothertransmembrane receptor Kremen into a trimer that can be endocytosed. Many inland scholarshave used the hydroxycamptothecine (HCPT) to block the Wnt signaling in that HCPT can workas an agonist of DKK1. On this basis, we doubt that whether HCPT could exert the same effecton wnt singal in the epididymal white adipose tissue (eWAT) of mice, and then affect theiradipogenesis. With all those above, we chose C57BL/6J WT, TNF-α-/-, Leprdb/dband DT mice asanimal models for HCPT interference experiment. Through the data of body weight, pathologicalfigure, gene and protein expression, we explored the effects of HCPT on eWAT of mice withdifferent genotypes. The results are showed below:1. The data of non-interfering mice showed that, the body weight and the adipocyte size ofall mice grew with age, and the Leprdb/dband DT mice that deficiency of leptin receptor (obesemice for short) showed a more obvious change compare to the WT and TNF-α-/-mice (lean micefor short). It was not seen the characteristics of obesity in TNF-α-/-mice even when they were6week old, and a possible explanation is that deficiency of TNF-α can not give rise to obesity onchow diet. While obese mice showed the increase of body weight only when they were3week old, and the degree of increase of DT mice was higher than that of Leprdb/dbmice, whichillustrated that deficiency of TNF-α can enhance the level of obesity in genetic obese mice, inturn, we can say that TNF-α enhance or help Wnt/β-catenin signaling pathway to inhibit obesity.2. Comprehensive comparison of the relative gene expression of eWAT both innon-interfering and saline injected mice, we found that the mRNA level of Wnt10b in obese micewas higher than that in lean mice, while the expression of adipogenesis relative factor C/EBPβ,PPARγ, C/EBPα and Adiponectin were lower. By the result above, we speculated that there didexist a negative feedback regulation mechanism in obese mice to defend themselves to developmore serious obesity.3. In vivo, all mice injected HCPT displayed a decrease in their body weight and adipocytesize. In addition, HCPT could downregulate the expression of factors related to Wnt/β-cateninsignaling pathway such as Wnt10b, LRP5and β-catenin, while to some extent, TNF-α helped toenhance the effect of HCPT. What’s more, HCPT could increase the mRNA level of C/EBPβwhen reduce the expression of PPARγ and C/EBPα, and the inhition effect exceeded thepromotion of adipogenesis arised from blocking the Wnt/β-catenin signaling pathway.In conclusion, HCPT has effects on the eWAT of mice with different genotypes. To bespecific, HCPT can inhibit the Wnt/β-catenin signaling pathway in eWAT while inhibiting theadipogenesis. So, it can be concluded that HCPT influences the eWAT through kinds ofcomplicated signal pathways rather than single pathway.