Association of β-Catenin with Fat Accumulation in 3T3-L1 Adipocytes and Human Population

Abstract

The major function of adipocytes is to store fat in the form of triglycerides. One of the signaling pathways known to affect adipogenesis, i.e. fat formation, is the WNT/β-catenin pathway which inhibits the expression and activity of key regulators of adipogenesis. The purpose of this research is to find genes among the WNT/β-catenin pathway which regulate adipogenesis by using small interfering (si) RNA and to find the association of single nucleotide polymorphisms (SNPs) of the gene with serum triglyceride levels in the human population. To elucidate the effects of β-catenin siRNA on adipogenesis key factors, PPARγ and C/EBPα, we performed real-time PCR and western blotting experiments for the analyses of mRNA and protein levels. It was found that the siRNA-mediated knockdown of β-catenin upregulates adipogenesis key factors. However, upstream regulators of the WNT/β-catenin pathway, such as DVL2 and LRP6, had no significant effects compared to β-catenin. These results indicate that β-catenin is a candidate gene for human fat accumulation. In general, serum triglyceride level is a good indicator of fat accumulation in humans. According to statistical analyses of the association between serum triglyceride level and SNPs of β-catenin,-10,288 C>T SNP (rs7630377) in the promoter region was significantly associated with serum triglyceride levels (p<0.05) in 290 Korean subjects. On the other hand, serum cholesterol levels were not significantly associated with SNPs of the β-catenin gene. The results of this study showed that β-catenin is associated with fat accumulation both in vitro and in the human population.