title: Active form Notch4 promotes the proliferation and differentiation of 3T3-L1 preadipocytes.
abstract: Adipose tissue is composed of adipocytes, which differentiate from precursor cells in a process called adipogenesis. Many signal molecules are involved in the 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. To elucidate the role of Notch4 in adipogenesis, the human active form Notch4 (N4IC) was transiently transfected into 3T3-L1 cells. The expression of HES1, Hey1, C/EBPδ and PPARγ was up-regulated, and the expression of Pref-1, an adipogenic inhibitor, was down-regulated. To further characterize the effect of N4IC in adipogenesis, stable cells expressing human N4IC were established. The expression of N4IC promoted proliferation and enhanced differentiation of 3T3-L1 cells compared with those of control cells. These data suggest that N4IC promoted proliferation through modulating the ERK pathway and the cell cycle during the early stage of 3T3-L1 adipogenesis and facilitated differentiation through up-regulating adipogenic genes such as C/EBPα, PPARγ, aP2, LPL and HSL during the middle and late stages of 3T3-L1 adipogenesis.
authors.affiliation: Institute of Molecular Biology and Department of Life Science, National Chung Cheng University, Chiayi 621, Taiwan, ROC.
authors.forename: Peng-Yeh
authors.initials: PY
authors.lastname: Lai
authors.forename: Chong-Bin
authors.initials: CB
authors.lastname: Tsai
authors.forename: Min-Jen
authors.initials: MJ
authors.lastname: Tseng
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology*; D050156:Adipogenesis / Q000235:genetics*; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D049109:Cell Proliferation; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics; D051379:Mice; D047495:PPAR gamma / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D000074562:Receptor, Notch4; D051880:Receptors, Notch / Q000235:genetics / Q000502:physiology*; D002787:Sterol Esterase / Q000235:genetics
chemical_list: D022763:CCAAT-Enhancer-Binding Protein-alpha; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; C106075:NOTCH4 protein, human; D047495:PPAR gamma; D011518:Proto-Oncogene Proteins; D000074562:Receptor, Notch4; D051880:Receptors, Notch; D002787:Sterol Esterase; D008071:Lipoprotein Lipase