The Possible Interaction of Cyclooxygenase and Lipoxygenase Mediated Pathways in the Development of Adipogenesis
| Autor: | Yang, Hui-Ju, 楊惠汝 |
|---|---|
| Rok vydání: | 2014 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 102 The cyclooxygenase (COX) mediated pathways and lipoxygenase (LOX) mediated pathways have been reported to participate in the regulation of adipogenesis. However the interaction of COX and LOX mediated pathways remains to be elucidated. This study was conducted with the 3T3-L1 cells to examine the involvement and interaction of COX and LOX mediated pathways in regulation of adipogenesis. Our data showed that gene expressions of the COX-1 and COX-2 were significantly enhanced at the early stage of adipocyte differentiation period, but those of 5-LOX and 12/15-LOX were mainly expressed at adipocyte maturation periods (late adipogenesis stage). Treatment with the COX1/2 and/or non-selective LOX inhibitors during adipocyte differentiation period could significantly suppress the adipocyte differentiation indicated by Oil red O staining. In the meantime, it is noted that LOX inhibition could induce the prolong increase of the C/EBP-β and C/EBP-δ transcript levels after initiation of adipogenesis. However, the mRNA levels of C/EBPα and PPAR-γ were not affected by the LOX inhibitor. The non-selective LOX inhibition during adipocyte differentiation period could cause a prolong increase of COX-2 but not COX-1 mRNA levels from 1 hour to 3 hour after the induction of adipogenesis. LOX inhibition also increased the protein level of COX-2 at 1 day after the induction of adipogenesis and these may subsequently increase the COX downstream PGF2α production, which will attenuate the adipogenesis. The treatment of COX1/2 inhibitor alone and/or combined during adipogenesis period would not affect the 5-LOX or 12/15-LOX gene expression. In addition, the 3T3-L1cell morphology indicated by Electric cell-substrate impedance sensing (ECIS) will change immediately after induction of adipogenesis. Treatment with the non-selective LOX inhibitor during adipocyte differentiation periods would increase the rate and amplitude of the morphology change, which might subsequently shift cell morphology at maturation phase close to undifferentiated 3T3-L1cell morphology. Treatment with the non-selective LOX inhibitor before induction caused Prdm16 and Pgc1-α gene expression increased suddenly at early phase of adipogenesis. The Prdm16 and Pgc1-α were involved in the regulation of white adipocyte trans-differentiation to brown adipocyte. LOX inhibition also increased the UCP-1 expressed in matured 3T3-L1 adipocyte. Taken together, it is suggested that there are interaction existed in both the COX and LOX mediated pathways in the regulation of adipogenesis. In the early phase of adipogenesis, the activation of the C/EBP-β, C/EBP-δ and COX-2 which could be regulated by LOX-mediated signaling. This might involve in the development of brown-like adipocyte. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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