| Summary: | 博士 === 國立中正大學 === 分子生物研究所 === 102 === Obesity is an energy balance disorder in the modern world which resulting in excessive white adipose tissue accumulation. Adipose tissue is composed of adipocytes, which differentiates from precursor cells in a process called adipogenesis. Many signal molecules are involved in transcriptional control of adipogenesis, including the Notch pathway. Previous adipogenic studies of Notch have focused on Notch1 and HES1; however, the role of other Notch receptors in adipogenesis remains unclear. Q-RT-PCR analyses showed that the augmentation of Notch4 expression during the differentiation of 3T3-L1 preadipocytes was comparable to that of Notch1. Furthermore, Notch2 expression level was increased significantly in the early differentiation day. To elucidate the role of Notch2 and Notch4 in adipogenesis, the human active form Notch2 (N2IC) and Notch4 (N4IC) were transiently transfected into 3T3-L1 cells. The expression of Notch downstream genes, HES1 and Hey1 and proadipogenic genes, C/EBPδ and PPARγ, were upregulated in N4IC-transfected cells and the expression of Pref-1, an adipogenic inhibitor, was downregulated. To further characterize the effects of N2IC and N4IC in adipogenesis, stable 3T3-L1 cell lines expressing human N2IC or N4IC were established. The expression of N2IC suppressed proliferation and differentiation of 3T3-L1 cells. On the other hand, expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. Cell cycle and gene expression analyses showed that N2IC suppressed proliferation through cell cycle regulation and suppressed differentiation through downregulating electron transport genes. However, N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through upregulating cholesterol biosynthesis genes and adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stage of 3T3-L1 adipogenesis.
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